Use of chromen-4-one derivatives

ABSTRACT

The invention relates to the use of chrome-4-one derivatives of the formula I  
                 
 
where R 1  and R 2  may be identical or different and are selected from H, —C(═O)—R 7 , —C(═O)—OR 7 , alkyl groups, alkenyl groups, hydroxyalkyl groups and/or cycloalkyl groups and/or cycloalkenyl groups, R 3  is H or alkyl groups, R 4  is H or OR 8 , R 5  and R 6  are selected from —H, —OH, alkyl groups, alkenyl groups and hydroxyalkyl groups, and R 7  is H, alkyl groups, a polyhydroxyl compound, such as, preferably, an ascorbic acid radical or glycosidic radicals, and R 8  is H or alkyl groups, where at least two of the substituents R 1 , R 2  and R 4 —R 6  are different from H or at least one substituent from R 1  and R 2  is —C(═O)—R 7  or —C(═O)—OR 7 , for the care, preservation or improvement of the general state of the skin or hair.

The present invention relates to the use of chromen-4-one derivativesfor the care, preservation or improvement of the general state of theskin or hair and for prophylaxis against time- and/or light-inducedageing processes of the human skin or human hair and for the prophylaxisand/or treatment of skin diseases. The invention furthermore relates tocompositions having an effective content of chromen4-one derivatives. Inparticular, the present invention relates to cosmetic compositions forprophylaxis against ageing processes in the skin.

The human skin is subject to certain ageing processes, some of which areattributable to intrinsic processes (chronoageing) and some of which areattributable to exogenous factors (environmental, for examplephoto-ageing). In addition, temporary or even lasting changes to theskin picture can occur, such as acne, greasy or dry skin, keratoses,rosaceae, light-sensitive, inflammatory, erythematous, allergic orautoimmune-reactive reactions, such as dermatosis and photodermatosis.

The exogenous factors include, in particular, sunlight or artificialradiation sources having a comparable spectrum, and compounds which canbe formed by the radiation, such as undefined reactive photoproducts,which may also be free-radical or ionic. These factors also includecigarette smoke and the reactive compounds present therein, such asozone, free radicals, for example the hydroxyl free radical, singletoxygen and other reactive oxygen or nitrogen compounds which interferewith the natural physiology or morphology of the skin.

The influence of these factors can result, inter alia, in direct damageto the DNA of the skin cells and to the collagen, elastin orglycosaminoglycan molecules of the extracellular matrix, which areresponsible for the strength of skin. In addition, the signaltransduction chains, which are terminated by the activation ofmatrix-degrading enzymes, may be affected. Important representatives ofthese enzymes are the matrix metalloproteinases (MMPs, for examplecollagenases, gelatinases and stromelysins), whose activity isadditionally regulated by TIMPs (tissue inhibitors of matrixmetalloproteinases).

The consequences of the above-mentioned ageing processes are thinning ofthe skin, weaker interlacing of epidermis and dermis, and a reduction inthe number of cells and the supplying blood vessels. This results in theformation of fine lines and wrinkles, the skin becomes leathery, andpigment defects can occur.

The same factors also act on hair, where damage can likewise occur. Thehairs become brittle, less elastic and dull. The surface structure ofthe hairs is damaged.

Cosmetic or dermatological care products having properties which areclaimed to counter the processes described or comparable processes orreduce or reverse the harmful consequences thereof are frequentlydistinguished by the following specificproperties—free-radical-scavenging, antioxidative,inflammation-inhibiting or humectant. They prevent or reduce, interalia, the activity of matrix-degrading enzymes or regulate the newsynthesis of collagen, elastin or proteoglycans.

The use of antioxidants or free-radical scavengers in cosmeticcompositions is adequately known per se. Thus, the use of theantioxidative vitamin E in sunscreen formulations is usual.Nevertheless, the effect achieved is even here well short of thehoped-for effect.

Vitamin A and vitamin-A derivatives, such as retinoic acid, retinol andretinol esters, act on the differentiation of epithelial cells and aretherefore employed for the prophylaxis and treatment of numerousphenomena which impair the skin state, for example use against acne,psoriasis, senile keratosis, skin discoloration and wrinkles has beendescribed (cf., for example, WO 93/19743 and WO 02/02074).

However, a skin-irritant effect of retinol and derivatives is alsodescribed in the literature (for example WO 94/07462). These sideeffects restrict the use of retinol to narrowly limited areas, it beingnecessary to avoid over-dosing. There is therefore a demand for activeingredients which have a retinol-like spectrum of action, but do nothave the side effects described or at least only do so in reduced form.

Owing to the constantly increasing demand for active ingredients for thepreventative treatment of human skin and human hair against ageingprocesses and harmful environmental influences, the object of thepresent invention was to provide novel active ingredients which exhibitthe effects already mentioned at the outset, are sufficiently oxidation-and photostable and can readily be formulated. The compositions preparedtherewith should furthermore have as far as possible a low irritationpotential for the skin, as far as possible have a positive influence onwater binding in the skin, retain or increase skin elasticity and thuspromote smoothing of the skin. In addition, they should preferablycreate a pleasant skin feeling on application to the skin.

Surprisingly, it has now been found that certain chromen-2-onederivatives (chromone derivatives) are suitable as active ingredientshaving the profile described.

The present invention relates firstly to the use of at least onecompound of the formula I

or of a composition comprising at least one compound of the formula I,where

-   -   R¹ and R² may be identical or different and are selected from    -   H, —C(═O)—R⁷ and —C(═O)—OR⁷,    -   straight-chain or branched C₁- to C₂₀-alkyl groups,    -   straight-chain or branched C₃- to C₂₀-alkenyl groups,        straight-chain or branched C₁- to C₂₀-hydroxyalkyl groups, where        the hydroxyl group may be bonded to a primary or secondary        carbon atom of the chain and furthermore the alkyl chain may        also be interrupted by oxygen, and/or    -   C₃- to C₁₀-cycloalkyl groups and/or C₃- to C₁₂-cycloalkenyl        groups,    -   where the rings may each also be bridged by —(CH₂)_(n)— groups,        where n=1 to 3,    -   R³ is H or straight-chain or branched C₁- to C₂₀-alkyl groups,    -   R⁴is H or —OR⁸,    -   R⁵ and R⁶ may be identical or different and are selected from        -   —H and —OH,        -   straight-chain or branched C₁- to C₂₀-alkyl groups,        -   straight-chain or branched C₃- to C₂₀-alkenyl groups,        -   straight-chain or branched C₁- to C₂₀-hydroxyalkyl groups,            where the hydroxyl group may be bonded to a primary or            secondary carbon atom of the chain and furthermore the alkyl            chain may also be interrupted by oxygen, and    -   R⁷ is H, straight-chain or branched C₁- to C₂₀-alkyl groups, a        polyhydroxyl compound, such as, preferably, an ascorbic acid        radical or glycosidic radicals, and    -   R⁸ is H or straight-chain or branched C₁- to C₂₀-alkyl groups,    -   where at least two of the substituents R¹, R² and R⁴—R⁶ are        different from H or at least one substituent from R¹ and R² is        —C(═O)—R⁷ or —C(═O)—OR⁷,    -   for the care, preservation or improvement of the general state        of the skin or hair.

For the purposes of the present invention, the term “compound of theformula I” basically also includes the salts of the compounds of theformula I. The preferred salts here include, in particular, alkali metaland alkaline earth metal salts as well as ammonium salts, but inparticular sodium and potassium salts.

The present invention furthermore relates to a composition comprising atleast one compound of the formula I containing radicals as definedabove, and at least one further skin-care ingredient and at least onecarrier which is suitable for topical applications.

Uses which are preferred in accordance with the invention of thecompounds of the formula I or of compositions comprising at least onecompound of the formula I are, in particular, the use for prophylaxisagainst time- and/or light-induced ageing processes of the human skin orhuman hair, in particular for prophylaxis against dry skin, wrinkleformation and/or pigment defects, and/or for the reduction or preventionof the harmful effects of UV rays on the skin, and for prophylaxisagainst or reduction of skin unevenness, such as wrinkles, fine lines,rough skin or large-pored skin.

Uses which are preferred in accordance with the invention of thecompounds of the formula I or of compositions comprising at least onecompound of the formula I are furthermore the use for the prophylaxisand/or prevention of premature skin ageing, in particular for theprophylaxis and/or prevention of light- or ageing-induced wrinkling ofthe skin, for the reduction of pigmentation and keratosis actinica, andfor the prophylaxis and/or treatment of all diseases which areassociated with normal skin ageing or light-induced ageing of the skin,and for the prophylaxis and/or treatment of skin diseases which areassociated with defective keratinisation relating to differentiation andcell proliferation, in particular for the treatment of acne vulgaris,acne comedonica, polymorphic acne, acne rosaceae, nodular acne, acneconglobata, age-related acne, acne occurring as a side effect, such asacne solaris, medicament-related acne or acne professionalis, for thetreatment of other defects of keratinisation, in particular ichthyosis,ichthyosiform states, Darier's disease, keratosis palmoplantaris,leukoplasia, leukoplasiform states, skin and mucosal (buccal) eczema(lichen), for the treatment of other skin diseases which are associatedwith defective keratinisation and have an inflammatory and/orimmunoallergic component, and in particular all forms of psoriasisrelating to the skin, mucous membranes and finger- and toenails, andpsoriatic rheumatism and skin atopy, such as eczema, or respiratoryatopy, or also hypertrophy of the gums, and for the prophylaxis and/ortreatment of all benign or malignant excrescence of the dermis orepidermis, which may be of viral origin, such as verruca vulgaris,verruca plana, epidermodysplasia verruciformis, oral papillomatosis,papillomatosis florida, and excrescence which may be caused by UVradiation, in particular epithelioma baso-cellulare and epitheliomaspinocellulare.

The present invention also relates to the use of the compounds of theformula I for the preparation of compositions which are suitable for theabove-mentioned uses.

The compositions here are usually either compositions which can be usedtopically, for example cosmetic or dermatological formulations, or foodsor food supplements. In this case, the compositions comprise acosmetically or dermatologically or food-suitable carrier and, dependingon the desired property profile, optionally further suitableconstituents.

The use according to the invention of chromen-4-one derivatives of thegeneral formula I in compositions offers, inter alia, protection againstdamage caused directly or indirectly by UV radiation or by processescaused by reactive compounds, such as, for example, skin ageing, loss ofskin moisture, loss of skin elasticity, formation of wrinkles or foldsor of pigment defects or senile keratosis.

The present invention furthermore relates to the use of theabove-mentioned compositions for the prevention of undesired changes tothe skin picture, such as, for example, acne or greasy skin, keratoses,light-sensitive, inflammatory, erythema tous, allergic orautoimmune-reactive reactions.

However, the compounds and compositions according to the inventionpreferably also serve to calm sensitive and irritated skin, for thepreventative regulation of collagen, hyaluronic acid and elastinsynthesis, stimulation of DNA synthesis, in particular in the case ofdeficient or hypoactive skin states, regulation of the transcription andtranslation of matrix-degrading enzymes, in particular of MMPs, increasein cell regeneration and regeneration of the skin, increase in theskin's own protective and repair mechanisms for DNA, lipids and/orproteins.

Preferred compounds of the formula I are characterised in that R³ is Hand R⁴ is OH, since the action potential of representatives of thisclass of com-pound is particularly high in the above-mentioned sense.If, in addition, at least one of the radicals R⁵ and R⁶ is OH, thesepreferred compounds, in addition to the above-mentioned properties,additionally have an anti-oxidant potential. They can thereforesimultaneously function as anti-oxidant in compositions.

Other preferred compounds of the formula I are characterised in that R⁵and R⁶ are H. In this case, the radicals R³ and R⁴ are freelyaccessible, which, as assumed, is advantageous for interaction withenzymes involved in the effects mentioned.

Likewise preferred compounds of the formula I are characterised in thatone of the radicals R¹ and R² is H and the other radical is —C(═O)—R⁷,—C(═O)—OR⁷ or a straight-chain or branched C₁- to C₂₀-alkyl group.

In addition, compounds which are preferred in accordance with theinvention have advantages on incorporation into the compositions:

-   -   mono- and/or oligoglycosyl radicals improve the water solubility        of the compounds to be employed in accordance with the        invention;    -   straight-chain or branched C₁- to C₂₀-alkoxy groups, in        particular the long-chain alkoxy functions, such as        ethylhexyloxy groups, increase the oil solubility of the        compounds;        i.e. the hydrophilicity or lipophilicity of the compounds        according to the invention can be increased through a suitable        choice of the substituents.

Glycosidic radicals which can be employed are in particular mono- oroligosaccharide radicals. Preference is given here to hexosyl radicals,in particular ramnosyl radicals and glucosyl radicals. However, otherhexosyl radicals, for example allosyl, altrosyl, galactosyl, gulosyl,idosyl, mannosyl and talosyl, may also advantageously be used. It mayalso be advantageous to use pentosyl radicals. The glycosyl radicals maybe linked to the basic structure by means of an α- or β-glycosidic link.A preferred disaccharide is, for example,6-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranoside.

However, in likewise preferred embodiments of the invention, thecompositions according to the invention may also comprise compounds ofthe formula I which are sparingly soluble or insoluble in thecomposition matrix. In this case, the compounds are preferably dispersedin finely divided form in the cosmetic composition.

Particular preference is given to the use of compounds selected from thecompounds of the formulae Ia-In:

Applications of structurally related compounds are known from theliterature:

The use of certain 2-(alkyl)carboxyl- or 2-(alkyl)phenyl-substitutedchromen-4-one derivatives in combination with divalent zinc inpharmaceutical and cosmetic compositions is disclosed in EP-A-0 304 802.The compositions are suitable for the treatment of skin, in particularfor the treatment of dermatoses, including atopic eczema.

EP-A-0 424 444 discloses the use of salts of chromonecarboxylic acid incosmetics for combating skin ageing. The compound exhibits aUV-filtering action here and.has the following effects in animalexperiments: the proportion of bound lipids in the skin increases, theproportion of soluble collagen in the skin is increased, the resistanceof the skin to the effects of the fibroplatic proteases collagenase andelastase is increased.

U.S. Pat No. 6,019,992 discloses cosmetic compositions which comprise4-chromanone and are suitable for the treatment of aged. dry or wrinkledskin. It is shown here that 4-chromanone promotes cell differentiationand stimulates lipid production in keratinocyte cultures.

EP-A-1 216 692 discloses the use of 2-methyl-2-(β-carboxyethyl)chromanderivatives in cosmetic compositions. The said compositions areparticularly suitable for prophylaxis against ageing processes of skinand hair and for prophylaxis against dry skin, wrinkle formation andpigment defects.

Compositions for topical application which comprise chromonederivatives, such as, for example, chromone, 7-hydroxychromone,7-methoxychromone, 5,7-dihydroxy-2-methylchromone,3-methyl-2-butenyloxychromone, 3-acetyl-5,7-dihydroxy-2-methylchromone,5-hydroxychromone, -n-pentyl 7-methoxychromone-2-carboxylate, n-undecyl5-methoxychromone-2-carboxylate, 5-hydroxy-7-methoxy-2-methylchromone,7-methoxychromone-2-carboxylic acid, n-pentylchromone-2-carboxylic acid,5-methoxychromone and chromone-2-carboxylic acid, are disclosed inJapanese patent application JP 05/301813. The chromone derivatives actas skin-tolerated tyrosinase inhibitors which reduce hyperpigmentationof the skin.

Japanese patent application JP 09/188608 discloses the use ofsubstituted chromone derivatives, such as, in particular,5,7-dihydroxychromones, 7-methoxychromones,5-hydroxy-7-methoxy-2-methylchromone and 5-hydroxy-2-methylchromone, asactive ingredient against grey hair. The action here is attributed toactivation of the coloured pigment-forming cells and the increase inmelanogenesis.

A composition against skin ageing comprising chromone derivatives whichare substituted in the 2-position by C₁₋₁₅-alkyl and have H, OH oralkoxy substitution in the 7-position, in combination with aminopropanolderivatives is disclosed in JP 10/194919.

Cosmetic compositions which comprise substituted chromone derivatives,such as, for example, 2-(1-ethylpentyl)chromone, 5,7-dihydroxychromones,7-methoxychromones, 5-hydroxy-7-methoxy-2-methylchromone and5-hydroxy-2-methylchromone, and aromatic compounds having a meltingpoint of -10C or above are disclosed in JP 10/114640. The chromonederivative here simplifies incorporation of the aromatic compound intothe cosmetic formulation.

The compounds of the formula I are typically employed in accordance withthe invention in amounts of from 0.01 to 20% by weight, preferably inamounts of from 0.1% by weight to 10% by weight and particularlypreferably in amounts of from 1 to 8% by weight. The person skilled inthe art has absolutely no difficulties in selecting the amountcorrespondingly depending on the intended action of the composition.

The protective action against oxidative stress or against the effect offree radicals can.thus be further improved if the compositions compriseone or more further antioxidants, where the person skilled in the arthas absolutely no difficulties in selecting antioxidants having asuitably fast or time-delayed action.

In a preferred embodiment of the present invention, at least one furtherskin-care ingredient is one or more antioxidants and/or vitamins.

For the above-mentioned reasons, it is particularly preferred here forthe composition to comprise no retinol derivative.

There are many proven substances known from the specialist literaturewhich can be used as antioxidants, for example amino acids (for exampleglycine, histidine, tyrosine, tryptophan) and derivatives thereof,imidazoles (for example urocanic acid) and derivatives thereof,peptides, such as D,L-carnosine, D-carnosine, L-carnosine andderivatives thereof (for example anserine), carotinoids, carotenes (forexample α-carotene, β-carotene, lycopene) and derivatives thereof,chlorogenic acid and derivatives thereof, lipoic acid and derivativesthereof (for example dihydrolipoic acid), aurothioglucose,propylthiouracil and other thiols (for example thioredoxin, glutathione,cysteine, cystine, cystamine and the glycosyl, N-acetyl, methyl, ethyl,propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleyl,cholesteryl and glyceryl esters thereof) and salts thereof, dilaurylthiodipropionate, distearyl thiodipropionate, thiodipropionic acid andderivatives thereof (esters, ethers, peptides, lipids, nucleotides,nucleosides and salts), and sulfoximine compounds (for examplebuthionine sulfoximines, homocysteine sulfoximine, buthionine sulfones,penta-, hexa- and heptathionine sulfoximine) in very low tolerated doses(for example pmol to μmol/kg), furthermore (metal) chelating agents (forexample α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin),α-hydroxy acids (for example citric acid, lactic acid, malic acid),humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTAand derivatives thereof, unsaturated fatty acids and derivativesthereof, vitamin C and derivatives (for example ascorbyl palmitate,magnesium ascorbyl phosphate, ascorbyl acetate), tocopherols andderivatives (for example vitamin E acetate), and coniferyl benzoate ofbenzoin resin, rutinic acid and derivatives thereof, α-glycosylrutin,ferulic acid, furfurylideneglucitol, carnosine, butyihydroxytoluene,butyihydroxyanisole, nordihydroguaiaretic acid, trihydroxybutyrophenone,quercetin, uric acid and derivatives thereof, mannose and derivativesthereof, zinc and derivatives thereof (for example ZnO, ZnSO₄), seleniumand derivatives thereof (for example selenomethionine), stilbenes andderivatives thereof (for example stilbene oxide, trans-stil-bene oxide).

Mixtures of antioxidants are likewise suitable for use in the cosmeticcompositions according to the invention. Known and commercial mixturesare, for example, mixtures comprising, as active ingredients, lecithin,L-(+)-ascorbyl palmitate and citric acid (for example Oxynex® AP),natural tocopherols, L-(+)-ascorbyl palmitate, L-(+)-ascorbic acid andcitric acid (for example Oxynex® K LIQUID), tocopherol extracts fromnatural sources, L-(+)-ascorbyl palmitate, L-(+)-ascorbic acid andcitric acid (for example Oxynex® L LIQUID), DL-α-tocopherol,L-(+)-ascorbyl palmitate, citric acid and lecithin (for example Oxynex®LM) or butylhydroxytoluene (BHT), L-(+)-ascorbyl palmitate and citricacid (for example Oxynex® 2004). Anti-oxidants of this type are usuallyemployed with compounds of the formula I in compositions of this type inratios in the range from 1000:1 to 1:1000, preferably in amounts of from100:1 to 1:100.

The compositions according to the invention may comprise vitamins asfurther ingredients. The cosmetic compositions according to theinvention preferably comprise vitamins and vitamin derivatives selectedfrom vitamin B, thiamine chloride hydrochloride (vitamin B₁), riboflavin(vitamin B₂), nicotinamide, vitamin C. (ascorbic acid), vitamin D,ergocalciferol (vitamin D₂), vitamin E, DL-α-tocopherol, tocopherol Eacetate, tocopherol hydrogensuccinate, vitamin K₁, esculin (vitamin Pactive ingredient), thiamine (vitamin B₁), nicotinic acid (niacin),pyridoxine, pyridoxal, pyridoxamine (vitamin B₆), pantothenic acid,biotin, folic acid and cobalamine (vitamin B₁₂), particularly preferablyvitamin C and derivatives thereof, DL-α-tocopherol, tocopherol Eacetate, nicotinic acid, pantothenic acid and biotin. Vitamins areusually employed here with compounds of the formula I in ratios in therange from 1000:1 to 1:1000, preferably in amounts of from 100:1 to1:100.

Of the phenols having an antioxidative action, the polyphenols, some ofwhich are naturally occurring, are of particular interest forapplications in the pharmaceutical, cosmetic or nutrition sector. Forexample, the flavonoids or bioflavonoids, which are principally known asplant dyes, frequently have an antioxidant potential. K. Lemanska, H.Szymusiak, B. Tyrakowska, R. Zielinski, I.M.C.M. Rietjens; CurrentTopics in Biophysics 2000, 24(2), 101-108, are concerned with effects ofthe substitution pattern of mono- and dihydroxyflavones. It is observedtherein that dihydroxyflavones containing an OH group adjacent to theketo function or OH groups in the 3′,4′- or 6,7- or 7,8-position haveantioxidative properties, while other mono- and dihydroxyflavones insome cases do not have antioxidative properties.

Quercetin (cyanidanol, cyanidenolon 1522, meletin, sophoretin, ericin,3,3′,4′,5,7-pentahydroxyflavone) is frequently mentioned as aparticularly effective antioxidant (for example C. A. Rice-Evans, N. J.Miller, G. Paganga, Trends in Plant Science 1997, 2(4), 152-159). K.Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, A. E. M. F.Soffers, I. M. C. M. Rietjens; Free Radical Biology&Medicine 2001,31(7), 869-881, have investigated the pH dependence of the antioxidantaction of hydroxyflavones. Quercetin exhibits the greatest activityamongst the structures investigated over the entire pH range.

Suitable antioxidants are furthermore compounds of the formula II

where R¹ to R¹⁰ may be identical or different and are selected from

-   -   H    -   OR¹¹    -   straight-chain or branched C₁- to C₂₀-alkyl groups,    -   straight-chain or branched C₃- to C₂₀-alkenyl groups,    -   straight-chain or branched C₁- to C₂₀-hydroxyalkyl groups, where        the hydroxyl group may be bonded to a primary or secondary        carbon atom of the chain and furthermore the alkyl chain may        also be interrupted by oxygen, and/or    -   C₃- to C₁₀-cycloalkyl groups and/or C₃- to C₁₂-cycloalkenyl        groups,    -   where the rings may each also be bridged by —(CH₂)_(n)— groups,    -   where n=1 to 3,    -   where all OR¹¹ are, independently of one another,        -   OH        -   straight-chain or branched C₁- to C₂₀-alkoxy groups,        -   straight-chain or branched C₃- to C₂₀-alkenyloxy groups,        -   straight-chain or branched C₁- to C₂₀-hydroxyalkoxy groups,            where the hydroxyl group(s) may be bonded to a primary or            secondary carbon atom of the chain and furthermore the alkyl            chain may also be interrupted by oxygen, and/or        -   C₃- to C₁₀-cycloalkoxy groups and/or C₃- to            C₁₂-cycloalkenyloxy groups, where the rings may each also be            bridged by —(CH₂)_(n)— groups, where n=1 to 3, and/or        -   mono- and/or oligoglycosyl radicals,    -   with the proviso that at least 4 radicals from R¹ to R⁷ are OH        and that the molecule contains at least two pairs of adjacent        —OH groups,    -   or R², R⁵ and R⁶ are OH and the radicals R¹, R³, R⁴ and R⁷⁻¹⁰        are H,        as described in the earlier German patent application DE        10244282.7.

Besides the advantages mentioned above, the advantages of thecompositions according to the invention comprising at least oneantioxidant here are, in particular, the antioxidant action and the goodskin tolerability. In addition, the compounds described here arepreferably colourless or have only a weak colour and thus only result inslight discoloration of the compositions, or none at all. Of particularadvantage is the particular action profile of the compounds of theformula II, which is evident in the DPPH assay in a high capacity forscavenging free radicals (EC₅₀), a time-delayed action (T_(EC50)>120min) and thus a moderate to high anti-free-radical efficiency (AE). Inaddition, the compounds of the formula I combine antioxidativeproperties with UV absorption in the UV-A and/or UV-B region in themolecule. Preference is therefore also given to compositions comprisingat least one compound of the formula II which is characterised in thatat least two adjacent radicals of the radicals R¹ to R⁴ are OH and atleast two adjacent radicals of the radicals R⁵ to R⁷ are OH.Particularly preferred compositions comprise at least one compound ofthe formula II. which is characterised in that at least three adjacentradicals of the radicals R¹ to R⁴ are OH, preferably with the radicalsR¹ to R³ being OH.

In order that the compounds of the formula I are able to develop theirpositive action as free-radical scavengers on the skin particularlywell, it may be preferred to allow the compounds of the formula I topenetrate into deeper skin layers. Several possibilities are availablefor this purpose. Firstly, the compounds of the formula I can have anadequate lipophilicity in order to be able to penetrate through theouter skin layer into epidermal layers. As a further possibility,corresponding transport agents, for example liposomes, which enabletransport of the compounds of the formula I through the outer skinlayers may also be provided in the composition. Finally, systemictransport of the compounds of the formula I is also conceivable. Thecomposition is then designed, for example, in such a way that it issuitable for oral administration.

It is also advantageous to -administer the compounds of the formula IIin encapsulated form, for example as cellulose or chitin capsules, ingelatine or wax matrices or encapsulated with cyclodextrins.

It is assumed that the preferred compounds of the formula I also act asenzyme inhibitors. They presumably inhibit protein kinases, elastase,aldose reductase and hyaluronidase, and therefore enable the intactnessof the basic substance of vascular sheaths to be maintained.Furthermore, they presumably inhibit non-specifically catechol O-methyltransferase, causing the amount of available catecholamine and thus thevascular strength to be increased. Furthermore, they are thought toinhibit AMP phosphodiesterase, giving the substances potential forinhibiting thrombocyte aggregation.

Owing to these properties, the compositions according to the inventionare, in general, suitable for immune protection and for the protectionof DNA and RNA. In particular, the compositions are suitable for theprotection of DNA and RNA against oxidative attack, against freeradicals and against damage due to radiation, in particular UVradiation. A further advantage of the compositions according to theinvention is cell protection, in particular protection of Langerhanscells against damage due to the above-mentioned influences. All theseuses and the use of the compounds of the formula I for the preparationof compositions which can be employed correspondingly are expressly alsoa subject-matter of the present invention.

In particular, preferred compositions according to the invention arealso suitable for the treatment of skin diseases associated with adefect in keratinisation which affects differentiation and cellproliferation, in particular for the treatment of acne vulgaris, acnecomedonica, polymorphic acne, acne rosaceae, nodular acne, acneconglobata, age-induced acne, acne which arises as a side effect, suchas acne solaris, medicament-induced acne or acne professionalis, for thetreatment of other defects in keratinisation, in particular ichthyosis,ichthyosiform states, Darier's disease, keratosis palmoplantaris,leucoplasia, leucoplasiform states, herpes of the skin and mucousmembrane (buccal) (lichen), for the treatment of other skin diseasesassociated with a defect in keratinisation and which have aninflammatory and/or immunoallergic component and in particular all formsof psoriasis which affect the skin, mucous membranes and fingers andtoenails, and psoriatic rheumatism and skin atopy, such as eczema orrespiratory atopy, or hypertrophy of the gums, it furthermore beingpossible for the compounds to be used for some inflammations which arenot associated with a defect in keratinisation, for the treatment of allbenign or malignant excrescence of the dermis or epidermis, which may beof viral origin, such as verruca vulgaris, verruca plana,epidermodysplasia verruciformis, oral papillomatosis, papillomatosisflorida, and excrescence which may be caused by UV radiation, inparticular epithelioma baso-cellulare and epithelioma spinocellulare,for the treatment of other skin diseases, such as dermatitis bullosa anddiseases affecting the collagen, for the treatment of certain eyediseases, in particular corneal diseases, for overcoming or combatinglight-induced skin ageing associated with ageing, for reducingpigmentation and keratosis actinica and for the treatment of alldiseases associated with normal ageing or light-induced ageing, for theprevention or healing of wounds/scars of atrophy of the epidermis and/ordermis caused by locally or systemically applied corticosteroids and allother types of skin atrophy, for the prevention or treatment of defectsin wound healing, for the prevention or elimination of stretch markscaused by pregnancy or for the promotion of wound healing, for combatingdefects in tallow production, such as hyperseborrhoea in acne or simpleseborrhoea, for combating or preventing cancer-like states orpre-carcinogenic states, in particular promyelocytic leukaemia, for thetreatment of inflammatory diseases, such as arthritis, for the treatmentof all virus-induced diseases of the skin or other areas of the body,for the prevention or treatment of alopecia, for the treatment of skindiseases or diseases of other areas of the body with an immunologicalcomponent, for the treatment of cardiovascular diseases, such asarteriosclerosis or hypertension, and of non-insulin-dependent diabetes,and for the treatment of skin problems caused by UV radiation.

Compositions which are particularly preferred in accordance with theinvention also comprise UV filters besides the compounds of the formulaI.

Use of the dibenzoylmethane derivatives, which are particularlypreferred as UV-A filters, in combination with the compounds of theformula I gives rise to a further additional advantage: the UV-sensitivedibenzoylmethane derivatives are additionally stabilised by the presenceof the compounds of the formula I. The present invention thereforefurthermore relates to the use of the compounds of the formula I for thestabilisation of dibenzoylmethane derivatives in compositions.

In principle, all UV filters are suitable for combination with thecompounds of the formula I. Particular preference is given to UV filterswhose physiological acceptability has already been demonstrated. Bothfor UVA and UVB filters, there are many proven substances which areknown from the specialist literature, for example:

-   -   benzylidenecamphor derivatives, such as        3-(4′-methylbenzylidene)-dl-camphor (for example Eusolex® 6300),        3-benzylidenecamphor (for example Mexoryl® SD), polymers of        N-{(2 and 4)-[(2-oxoborn-3-ylidene)methyl]-benzyl}acrylamide        (for example Mexoryl® SW),        N,N,N-trimethyl-4-(2-oxoborn-3-ylidenemethyl)anilinium        methylsulfate (for example Mexoryl® SK) or        (2-oxoborn-3-ylidene)toluene-4-sulfonic acid (for example        Mexoryl® SL),    -   benzoyl- or dibenzoylmethanes, such as        1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione        (for. example Eusolex® 9020) or 4-isopropyl-dibenzoylmethane        (for example Eusolex® 8020),    -   benzophenones, such as 2-hydroxy-4-methoxybenzophenone (for        example Eusolex® 4360) or        2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its sodium        salt (for example Uvinul® MS-40),    -   methoxycinnamic acid esters, such as octyl methoxycinnamate (for        example Eusolex® 2292) or isopentyl 4-methoxycinnamate, for        example as a mixture of the isomers (for example Neo Heliopan® E        1000),    -   salicylate derivatives, such as 2-ethylhexyl salicylate (for        example Eusolex® OS), 4-isopropylbenzyl salicylate (for example        Megasol®) or 3,3,5-trimethylcyclohexyl salicylate (for example        Eusolex® HMS),    -   4-aminobenzoic acid and derivatives, such as 4-aminobenzoic        acid, 2-ethylhexyl 4-(dimethylamino)benzoate (for example        Eusolex® 6007) or ethoxylated ethyl 4-aminobenzoate (for example        Uvinul® P25),    -   phenylbenzimidazolesulfonic acids, such as        2-phenylbenzimidazole-5-sulfonic acid and potassium, sodium and        triethanolamine salts thereof (for example Eusolex® 232),        2,2-(1,4-phenylene)bisbenzimidazole4,6-disulfonic acid and salts        thereof (for example Neoheliopan® AP) or        2,2-(1,4-phenylene)bisbenzimidazole-6-sulfonic acid;    -   and further substances, such as        -   2-ethylhexyl 2-cyano-3,3-diphenylacrylate (for example            Eusolex® OCR),        -   3,3′-(1,4-phenylenedimethylene)bis(7,7-dimethyl-2-oxobicyclo[2.2.1]-hept-1-ylmethanesulfonic            acid and salts thereof (for example Mexoryl® SX),        -   2,4,6-trianilino-(p-carbo-2′-ethylhexyl-1            ′-oxy)-1,3,5-triazine (for example Uvinul® T 150) and        -   hexyl 2-(4-diethylamino-2-hydroxybenzoyl)benzoate (for            example Uvinul® UVA Plus, BASF).

The compounds mentioned in the list should only be regarded as examples.It is of course also possible to use other UV filters.

These organic UV filters are generally incorporated into cosmeticformulations in an amount of from 0.5 to 1.0 per cent by weight,preferably 1-8%.

Further suitable organic UV filters are, for example,

-   -   2-(2H-benzotriazol-2-yl)-4-methyl-6-(2-methyl-3-(1,3,3,3-tetramethyl-1-(trimethylsilyloxy)disiloxanyl)propyl)phenol        (for example Silatrizole®),    -   2-ethylhexyl        4,4′-[(6-[4-((1,1-dimethylethyl)aminocarbonyl)phenylamino]-1,3,5-triazine-2,4-diyl)diimino]bis(benzoate)        (for example Uvasorb® HEB),    -   α-(trimethylsilyl)-ω-[trimethylsilyl)oxy]poly[oxy(dimethyl [and        about 6% of        methyl[2-[p-[2,2-bis(ethoxycarbonyl]vinyl]phenoxy]-1-methyleneethyl]        and approximately 1.5% of        methyl[3-[p-[2,2-bis(ethoxycarbonyl)vinyl]-phenoxy]propenyl] and        from 0.1 to 0.4% of (methylhydrogen]silylene]] (n≈60) (CAS No.        207 574-74-1)    -   2,2′-methylenebis(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)-phenol)        (CAS No. 103 597-45-1)    -   2,2′-(1,4-phenylene)bis(1H-benzimidazole-4,6-disulfonic acid,        mono-sodium salt) (CAS No. 180 898-37-7),    -   2,4-bis{[4-(2-ethylhexyloxy)-2-hydroxy]phenyl}-6-(4-methoxyphenyl)-1,3,5-triazine        (CAS No. 103 59745-, 187 393-00-6) and    -   2-ethylhexyl        4,4′-[(6-[4-((1,1-dimethylethyl)aminocarbonyl)phenyl-amino]-1,3,5-triazine-2,4-diyl)diimino]bis(benzoate)        (for example Uvasorb® HEB).

Further suitable UV filters are also methoxyflavones corresponding tothe earlier German patent application DE 10232595.2.

Organic UV filters are generally incorporated into cosmetic formulationsin an amount of from 0.5 to 20 per cent by weight, preferably 1-15%.

Conceivable inorganic UV filters are those from the group consisting oftitanium dioxides, such as, for example, coated titanium dioxide (forexample E usolex® T-2000, Eusolex® T-AQUA), zinc oxides (for exampleSachtotec®), iron oxides and also cerium oxides. These inorganic UVfilters are generally incorporated into cosmetic compositions in anamount of from 0.5 to 20 per cent by weight, preferably 2-10%.

Preferred compounds having UV-filtering properties are3-(4′-methylbenzylidene)-dl-camphor,1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione,4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octylmethoxycinnamate, 3,3,5-trimethylcyclohexyl salicylate, 2-ethylhexyl4-(dimethylamino)benzoate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate,2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium andtriethanolamine salts.

Through combination of one or more compounds of the formula I withfurther UV filters, the protective action against harmful influences ofUV radiation can be optimised.

Optimised compositions may comprise, for example, the combination of theorganic UV filters 4′-methoxy-6-hydroxyflavone with1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione and3-(4′-methylbenzylidene)-dl-camphor. This combination gives rise tobroad-band protection, which can be supplemented by the addition ofinorganic UV filters, such as titanium dioxide microparticles.

All the said UV filters can also be employed in encapsulated form. Inparticular, it is advantageous to employ organic UV filters inencapsulated form. In detail, the following advantages arise:

-   -   The hydrophilicity of the capsule wall can be set independently        of the solubility of the UV filter. Thus, for example, it is        also possible to incorporate hydrophobic UV filters into purely        aqueous compositions. In addition, the oily impression on        application of the composition comprising hydrophobic UV        filters, which is frequently regarded as unpleasant, is        suppressed.    -   Certain UV filters, in particular dibenzoylmethane derivatives,        exhibit only reduced photostability in cosmetic compositions.        Encapsulation of these filters or compounds which impair the        photostability of these filters, such as, for example, cinnamic        acid derivatives, enables the photostability of the entire        composition to be increased.    -   Skin penetration by organic UV filters and the associated        potential for irritation on direct application to the human skin        is repeatedly being discussed in the literature. The        encapsulation of the corresponding substances which is proposed        here suppresses this effect.    -   In general, encapsulation of individual UV filters or other        ingredients enables composition problems caused by the        interaction of individual composition constituents with one        another, such as crystallisation processes, precipitation and        agglomerate formation, to be avoided since the interaction is        suppressed.

It is therefore preferred in accordance with the invention for one ormore of the above-mentioned UV filters to be in encapsulated form. It isadvantageous here for the capsules to be so small that they cannot beviewed with the naked eye. In order to achieve the above-mentionedeffects, it is furthermore necessary for the capsules to be sufficientlystable and the encapsulated active ingredient (UV filter) only to bereleased to the environment to a small extent, or not at all.

Suitable capsules can have walls of inorganic or organic polymers. Forexample, U.S. Pat No. 6,242,099 B1 describes the production of suitablecapsules with walls of chitin, chitin derivatives or polyhydroxylatedpolyamines. Capsules which can particularly preferably be employed inaccordance with the invention have walls which can be obtained by asol-gel process, as described in the applications WO 00/09652, WO00/72806 and WO 00/71084. Preference is again given here to capsuleswhose walls are built up from silica gel (silica; undefined siliconoxide hydroxide). The production of corresponding capsules is known tothe person skilled in the art, for example from the cited patentapplications, whose contents expressly also belong to the subject-matterof the present application.

The capsules are preferably present in compositions according to theinvention in amounts which ensure that the encapsulated UV filters arepresent in the composition in the above-indicated amounts.

The skin-protecting or skin-care active ingredients can in principle beany active ingredients known to the. person skilled in the art.

In an embodiment of the present invention, particularly preferred activeingredients are pyrimidinecarboxylic acids and/or aryl oximes.

Pyrimidinecarboxylic acids occur in halophilic microorganisms and play arole in osmoregulation of these organisms (E. A. Galinski et al., Eur.J. Biochem., 149 (1985) pages 135-139). Of the pyrimidinecarboxylicacids, particular mention should be made here of ectoine((S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) andhydroxyectoine((S,S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl4-pyrimidinecarboxylic acid)and derivatives thereof. These compounds stabilise enzymes and otherbiomolecules in aqueous solutions and organic solvents. Furthermore,they stabilise, in particular, enzymes against denaturing conditions,such as salts, extreme pH values, surfactants, urea, guanidiniumchloride and other compounds.

Ectoine and ectoine derivatives, such as hydroxyectoine, canadvantageously be used in medicaments. In particular, hydroxyectoine canbe employed for the preparation of a medicament for the treatment ofskin diseases. Other areas of application of hydroxyectoine and otherectoine derivatives are typically in areas in which, for example,trehalose is used as additive. Thus, ectoine derivatives, such ashydroxyectoine, can be used as protectant in dried yeast and bacteriacells. Pharmaceutical products, such as non-glycosylated,pharmaceutically active peptides and proteins, for example t-PA, canalso be protected with ectoine or its derivatives.

Of the cosmetic applications, particular mention should be made of theuse of ectoine and ectoine derivatives for the care of aged, dry orirritated skin. Thus, European patent application EP-A-0 671 161describes, in particular, that ectoine and hydroxyectoine are employedin cosmetic compositions, such as powders, soaps, surfactant-containingcleansing products, lipsticks, rouge, make-ups, care creams andsunscreen compositions.

Preference is given here to the use of a pyrimidinecarboxylic acid ofthe following formula II

in which R¹ is a radical H or C₁-8-alkyl, R² is a radical H orC₁-4-alkyl, and R³, R⁴, R⁵ and R⁶ are each, independently of oneanother, a radical from the group consisting of H, OH, NH₂ andC1-4-alkyl. Preference is given to the use of pyrimidinecarboxylic acidsin which R² is a methyl or ethyl group, and R¹ or R⁵ and R⁶ are H.Particular preference is given to the use of the pyrimidinecarboxylicacids ectoine ((S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylicacid) and hydroxyectoine((S,S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylicacid). The compositions according to the invention preferably comprisepyrimidinecarboxylic acids of this type in amounts of up to 15% byweight. The pyrimidinecarboxylic acids are preferably employed here inratios of from 100:1 to 1:100 with respect to the compounds of theformula I, with ratios in the range from 1:10 to 10:1 being particularlypreferred.

Of the aryl oximes, preference is given to the use of2-hydroxy-5-methyllaurophenone oxime, which is also known as HMLO, LPOor F5. Its suitability for use in cosmetic compositions is disclosed,for example, in DE-A-41 16 123. Compositions which comprise2-hydroxy-5-methyllaurophenone oxime are accordingly suitable for thetreatment of skin diseases which are accompanied by inflammation. It isknown that compositions of this type can be used, for example, for thetherapy of psoriasis, various forms of eczema, irritative and toxicdermatitis, UV dermatitis and further allergic and/or inflammatorydiseases of the skin and integumentary appendages. Compositionsaccording to the invention which, in addition to the compound of theformula I, additionally comprise an aryl oxime, preferably2-hydroxy-5-methyllaurophenone oxime, exhibit surprisinganti-inflammatory suitability. The compositions here preferably comprisefrom 0.01 to 10% by weight of the aryl oxime, it being particularlypreferred for the composition to comprise from 0.05 to 5% by weight ofaryl oxime.

All compounds or components which can be used in the compositions areeither known or commercially available or can be synthesised by knownprocesses. The preparation of the novel compounds of the formula I isdescribed below.

The one or more compounds of the formula I can be incorporated intocosmetic or dermatological compositions in the customary manner.Suitable compositions are those for external use, for example in theform of a cream, lotion or gel or as a solution which can be sprayedonto the skin. Suitable for internal use are administration forms suchas capsules, coated tablets, powders, tablet solutions or solutions.

Use forms of the compositions according to the invention that may bementioned are, for example, solutions, suspensions, emulsions, PITemulsions, pastes, ointments, gels, creams, lotions, powders, soaps,surfactant-containing cleansing preparations, oils, aerosols and sprays.Examples of other use forms are sticks, shampoos and showercompositions. Any desired customary carriers, assistants and, ifdesired, further active ingredients may be added to the composition.

Preferred assistants originate from the group consisting ofpreservatives, antioxidants, stabilisers, solubilisers, vitamins,colorants and odour improvers.

Ointments, pastes, creams and gels may comprise the customary carriers,for example animal and vegetable fats, waxes, paraffins, starch,tragacanth, cellulose derivatives, polyethylene glycols, silicones,bentonites, silica, talc and zinc oxide, or mixtures of thesesubstances.

Powders and sprays may comprise the customary carriers, for examplelactose, talc, silica, aluminium hydroxide, calcium silicate andpolyamide powder, or mixtures of these substances. Sprays mayadditionally comprise the customary propellants, for examplechlorofluorocarbons, propane/butane or dimethyl ether.

Solutions and emulsions may comprise the customary carriers, such assolvents, solubilisers and emulsifiers, for example water, ethanol,isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzylbenzoate, propylene glycol, 1,3-butyl glycol, oils, in particularcottonseed oil, peanut oil, wheatgerm oil, olive oil, castor oil andsesame oil, glycerol fatty acid esters, polyethylene glycols and fattyacid esters of sorbitan, or mixtures of these substances.

Suspensions may comprise the customary carriers, such as liquiddiluents, for example water, ethanol or propylene glycol, suspendingagents, for example ethoxylated isostearyl alcohols, polyoxyethylenesorbitol esters and polyoxyethylene sorbitan esters, microcrystallinecellulose, aluminium metahydroxide, bentonite, agar-agar and tragacanth,or mixtures of these substances.

Soaps may comprise the customary carriers, such as alkali metal salts offatty acids, salts of fatty acid monoesters, fatty acid proteinhydrolysates, isethionates, lanolin, fatty alcohol, vegetable oils,plant extracts, glycerol, sugars, or mixtures of these substances.

Surfactant-containing cleansing products may comprise the customarycarriers, such as salts of fatty alcohol sulfates, fatty alcohol ethersulfates, sulfosuccinic acid monoesters, fatty acid proteinhydrolysates, isethionates, imidazolinium derivatives, methyl taurates,sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, fattyalcohols, fatty acid glycerides, fatty acid diethanolamides, vegetableand synthetic oils, lanolin derivatives, ethoxylated glycerol fatty acidesters, or mixtures of these substances.

Face and body oils may comprise the customary carriers, such assynthetic oils, such as fatty acid esters, fatty alcohols, siliconeoils, natural oils, such as vegetable oils and oily plant extracts,paraffin oils or lanolin oils, or mixtures of these substances.

Further typical cosmetic use forms are also lipsticks, lip-care sticks,mascara, eyeliner, eye-shadow, rouge, powder make-up, emulsion make-upand wax make-up, and sunscreen, pre-sun and after-sun preparations.

The preferred composition forms according to the invention include, inparticular, emulsions.

Emulsions according to the invention are advantageous and comprise, forexample, the said fats, oils, waxes and other fatty. substances, as wellas water and an emulsifier, as usually used for a composition of thistype.

The lipid phase may advantageously be selected from the following groupof substances:

-   -   mineral oils, mineral waxes;    -   oils, such as triglycerides of capric or caprylic acid,        furthermore natural oils, such as, for example, castor oil;    -   fats, waxes and other natural and synthetic fatty substances,        preferably esters of fatty acids with alcohols having a low        carbon number, for example with isopropanol, propylene glycol or        glycerol, or esters of fatty alcohols with alkanoic acids having        a low carbon number or with fatty acids;    -   silicone oils, such as dimethylpolysiloxanes,        diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms        thereof.

For the purposes of the present invention, the oil phase of theemulsions, oleogels or hydrodispersions or lipodispersions isadvantageously selected from the group consisting of esters of saturatedand/or unsaturated, branched and/or unbranched alkanecarboxylic acidshaving a chain length of from 3 to 30 carbon atoms and saturated and/orunsaturated, branched and/or unbranched alcohols having a chain lengthof from 3 to 30 carbon atoms, or from the group consisting of esters ofaromatic carboxylic acids and saturated and/or unsaturated, branchedand/or unbranched alcohols having a chain length of from 3 to 30 carbonatoms. Ester oils of this type can then advantageously be selected fromthe group consisting of isopropyl myristate, isopropyl palmitate,isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate,n-decyl oleate, isooctyl stearate, isononyl stearate, isononylisononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecylstearate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyloleate, erucyl erucate and synthetic, semi-synthetic and naturalmixtures of esters of this type, for example jojoba oil.

The oil phase may furthermore advantageously be selected from the groupconsisting of branched and unbranched hydrocarbons and waxes, siliconeoils, dialkyl ethers, or the group consisting of saturated andunsaturated, branched and unbranched alcohols, and fatty acidtriglycerides, specifically the triglycerol esters of saturated and/orunsaturated, branched and/or unbranched alkanecarboxylic acids having achain length of from 8 to 24, in particular 12-18, carbon atoms. Thefatty acid triglycerides may advantageously be selected, for example,from the group consisting of synthetic, semi-synthetic and natural oils,for example olive oil, sunflower oil, soya oil, peanut oil, rapeseedoil, almond oil, palm oil, coconut oil, palm kernel oil and the like.

Any desired mixtures of oil and wax components of this type may alsoadvantageously be employed for the purposes of the present invention. Itmay also be advantageous to employ waxes, for example cetyl palmitate,as the only lipid component of the oil phase.

The oil phase is advantageously selected from the group consisting of2-ethylhexyl isostearate, octyidodecanol, isotridecyl isononanoate,isoeicosane, 2-ethylhexyl cocoate, C₁₂₁₅-alkyl benzoate, caprylic/capricacid triglyceride and dicapryl ether.

Particularly advantageous are mixtures of C₁₂₋₁₅-alkyl benzoate and2-ethylhexyl isostearate, mixtures of C₁₂₋₁₅-alkyl benzoate andisotridecyl isononanoate, as well as mixtures of C₁₂₋₁₅-alkyl benzoate,2-ethylhexyl isostearate and isotridecyl isononanoate.

Of the hydrocarbons, paraffin oil, squalane and squalene mayadvantageously be used for the purposes of the present invention.

Furthermore, the oil phase may also advantageously have a content ofcyclic or linear silicone oils or consist entirely of oils of this type,although it is preferred to use an additional content of other oil-phasecomponents in addition to the silicone oil or the silicone oils.

The silicone oil to be used in accordance with the invention isadvantageously cyclomethicone (octamethylcyclotetrasiloxane). However,it is also advantageous for the purposes of the present invention to useother silicone oils, for example hexamethylcyclotrisiloxane,polydimethylsiloxane or poly(methylphenylsiloxane).

Also particularly advantageous are mixtures of cyclomethicone andisotridecyl isononanoate and of cyclomethicone and 2-ethylhexylisostearate.

The aqueous phase of the compositions according to the inventionoptionally advantageously comprises alcohols, diols or polyols having alow carbon number, and ethers thereof, preferably ethanol, isopropanol,propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethylor monobutyl ether, propylene glycol monomethyl, monoethyl or monobutylether, diethylene glycol monomethyl or monoethyl ether and analogousproducts, furthermore alcohols having a low carbon number, for exampleethanol, isopropanol, 1,2-propanediol or glycerol, and, in particular,one or more thickeners, which may advantageously be selected from thegroup consisting of silicon dioxide, aluminium silicates,polysaccharides and derivatives thereof, for example hyaluronic acid,xanthan gum, hydroxypropylmethylcellulose, particularly advantageouslyfrom the group consisting of the polyacrylates, preferably apolyacrylate from the group consisting of the so-called Carbopols, forexample Carbopol grades 980, 981, 1382, 2984 or 5984, in each caseindividually or in combination.

In particular, mixtures of the above-mentioned solvents are used. In thecase of alcoholic solvents, water may be a further constituent.

Emulsions according to the invention are advantageous and comprise, forexample, the said fats, oils, waxes and other fatty substances, as wellas water and an emulsifier, as usually used for a formulation of thistype.

In a preferred embodiment, the compositions according to the inventioncomprise hydrophilic surfactants.

The hydrophilic surfactants are preferably selected from the groupconsisting of the alkylglucosides, acyl lactylates, betaines and coconutamphoacetates.

The alkylglucosides are themselves advantageously selected from thegroup consisting of the alkylglucosides which are distinguished by thestructural formula

where R is a branched or unbranched alkyl radical having from 4 to 24carbon atoms, and where {overscore (DP)} denotes a mean degree ofglucosylation of up to 2.

The value {overscore (DP)} represents the degree of glucosidation of thealkylglucosides used in accordance with the invention and is defined as$\overset{\_}{DP} = {{{\frac{p_{1}}{100} \cdot 1} + {\frac{p_{2}}{100} \cdot 2} + {\frac{p_{3}}{100} \cdot 3} + \ldots} = {\Sigma{\frac{p_{i}}{100} \cdot i}}}$in which P₁, P₂, P₃ . . . p_(i) represent the proportion of mono-, di-,tri- . . . i-fold glucosylated products in per cent by weight. Productswhich are advantageous according to the invention are those havingdegrees of glucosylation of 1-2, particularly advantageously of from 1.1to 1.5, very particularly advantageously of 1.2-1.4, in particular of1.3.

The value DP takes into account the fact that alkylglucosides aregenerally, as a consequence of their preparation, in the form ofmixtures of mono- and oligoglucosides. A relatively high content ofmonoglucosides, typically in the order of 40-70% by weight, isadvantageous in accordance with the invention.

Alkylglycosides which are particularly advantageously used for thepurposes of the invention are selected from the group consisting ofoctyl glucopyranoside, nonyl glucopyranoside, decyl glucopyranoside,undecyl glucopyranoside, dodecyl glucopyranoside, tetradecylglucopyranoside and hexadecyl glucopyranoside.

It is likewise advantageous to employ natural or synthetic raw materialsand assistants or mixtures which are distinguished by an effectivecontent of the active ingredients used in accordance with the invention,for example Plantarene 1200 (Henkel KGaA), Oramix® NS 10 (Seppic).

The acyllactylates are themselves advantageously selected from the groupconsisting of the substances which are distinguished by the structuralformula

where R¹ is a branched or unbranched alkyl radical having from 1 to 30carbon atoms, and M⁺ is selected from the group consisting of the alkalimetal ions and the group consisting of ammonium ions which aresubstituted by one or more alkyl and/or one or more hydroxyalkylradicals, or corresponds to half an equivalent of an alkaline earthmetal ion.

For example, sodium isostearyl lactylate, for example the productPathionic® ISL from the American Ingredients Company, is advantageous.

The betaines are advantageously selected from the group consisting ofthe substances which are distinguished by the structural formula

where R² is a branched or unbranched alkyl radical having from 1 to 30carbon atoms.

R² is particularly advantageously a branched or unbranched alkyl radicalhaving from 6 to 12 carbon atoms.

For example, capramidopropylbetaine, for example the product Tego®Betain 810 from Th. Goldschmidt AG, is advantageous.

A coconut amphoacetate which is advantageous for the purposes of theinvention is, for example, sodium coconut amphoacetate, as availableunder the name Miranol® Ultra C₃₂ from Miranol Chemical Corp.

The compositions according to the invention are advantageouslycharacterised in that the hydrophilic surfactant(s) is (are) present inconcentrations of 0.01-20% by weight, preferably 0.05-10% by weight,particularly preferably 0.1-5% by weight, in each case based on thetotal weight of the composition.

For use, the cosmetic and dermatological compositions are applied insufficient amount to the skin and/or hair in the usual manner forcosmetics.

Cosmetic and dermatological compositions according to the invention mayexist in various forms. Thus, they may be, for example, a solution, awater-free composition, an emulsion or microemulsion of the water-in-oil(W/O) or oil-in-water (O/W) type, a multiple emulsion, for example ofthe water-in-oil-in-water (W/O/W) type, a gel, a solid stick, anointment or an aerosol. It is also advantageous to administer ectoinesin encapsulated form, for example in collagen matrices and otherconventional encapsulation materials, for example as celluloseencapsulations, in gelatine, wax matrices or liposomally encapsulated.In particular, wax matrices, as described in DE-A 43 08 282, have provenfavourable. Preference is given to emulsions. O/W emulsions areparticularly preferred. Emulsions, W/O emulsions and O/W emulsions areobtainable in a conventional manner.

Emulsifiers that can be used are, for example, the known W/O and O/Wemulsifiers. It is advantageous to use further conventionalco-emulsifiers in the preferred O/W emulsions according to theinvention.

Co-emulsifiers which are advantageous according to the invention are,for example, O/W emulsifiers, principally from the group consisting ofthe substances having HLB values of 11-16, very particularlyadvantageously having HLB values of 14.5-15.5, so long as the O/Wemulsifiers have saturated radicals R and R′. If the O/W emulsifiershave unsaturated radicals R and/or R′ or in the case of isoalkylderivatives, the preferred HLB value of such emulsifiers may also belower or higher.

It is advantageous to select the fatty alcohol ethoxylates from thegroup consisting of ethoxylated stearyl alcohols, cetyl alcohols,cetylstearyl alcohols (cetearyl alcohols). Particular preference isgiven to the following: polyethylene glycol (13) stearyl ether(steareth-13), polyethylene glycol (14) stearyl ether (steareth-14),polyethylene glycol (15) stearyl ether (steareth-15), polyethyleneglycol (16) stearyl ether (steareth-16), polyethylene glycol (17)stearyl ether (steareth-17), polyethylene glycol (18) stearyl ether(steareth-18), polyethylene glycol (19) stearyl ether (steareth-19),polyethylene glycol (20) stearyl ether (steareth-20), polyethyleneglycol (12) isostearyl ether (isosteareth-12), polyethylene glycol (13)isostearyl ether (isosteareth-13), polyethylene glycol (14) isostearylether (isosteareth-14), polyethylene glycol (15) isostearyl ether(isosteareth-15), polyethylene glycol (16) isostearyl ether(isosteareth-16), polyethylene glycol (17) isostearyl ether(isosteareth-17), polyethylene glycol (18) isostearyl ether(isosteareth-18), polyethylene glycol (19) isostearyl ether(isosteareth-19), polyethylene glycol (20) isostearyl ether(isosteareth-20), polyethylene glycol (13) cetyl ether (ceteth-13),polyethylene glycol (14) cetyl ether (ceteth-14), polyethylene glycol(15) cetyl ether (ceteth-15), polyethylene glycol (16) cetyl ether(ceteth-16), polyethylene glycol (17) cetyl ether (ceteth-17),polyethylene glycol (18) cetyl ether (ceteth-18), polyethylene glycol(19) cetyl ether (ceteth-19), polyethylene glycol (20) cetyl ether(ceteth-20), polyethylene glycol (13) isocetyl ether (isoceteth-13),polyethylene glycol (14) isocetyl ether (isoceteth-14), polyethyleneglycol (15) isocetyl ether (isoceteth-15), polyethylene glycol (16)isocetyl ether (isoceteth-16), polyethylene glycol (17) isocetyl-ether(isoceteth-17), polyethylene glycol (18) isocetyl ether (isoceteth-18),polyethylene glycol (19) isocetyl ether (isoceteth-19), polyethyleneglycol (20) isocetyl ether (isoceteth-20), polyethylene glycol (12)oleyl ether (oleth-12), polyethylene glycol (13) oleyl ether (oleth-13),polyethylene glycol (14) oleyl ether (oleth-14), polyethylene glycol(15) oleyl ether (oleth-15), polyethylene glycol (12) lauryl ether(laureth-12), polyethylene glycol (12) isolauryl ether (isolaureth-12),polyethylene glycol (13) cetylstearyl ether (ceteareth-13), polyethyleneglycol (14) cetylstearyl ether (ceteareth-14), polyethylene glycol (15)cetylstearyl ether (ceteareth-1 5), polyethylene glycol (16)cetylstearyl ether (ceteareth-16), polyethylene glycol (17) cetylstearylether (ceteareth-17), polyethylene glycol (18) cetylstearyl.ether(ceteareth-18), polyethylene glycol (19) cetylstearyl ether(ceteareth-19), polyethylene glycol (20) cetylstearyl ether(ceteareth-20).

It is furthermore advantageous to select the fatty acid ethoxylates fromthe following group:

-   -   polyethylene glycol (20) stearate, polyethylene glycol (21)        stearate, polyethylene glycol (22) stearate, polyethylene        glycol (23) stearate, polyethylene glycol (24) stearate,        polyethylene glycol (25) stearate, polyethylene glycol (12)        isostearate, polyethylene glycol (1.3) isostearate, polyethylene        glycol (14) isostearate, polyethylene glycol (15) isostearate,        polyethylene glycol (16) isostearate, polyethylene glycol (17)        isostearate, polyethylene glycol (18) isostearate, polyethylene        glycol (19) isostearate, polyethylene glycol (20) isostearate,        polyethylene glycol (21) isostearate, polyethylene glycol (22)        isostearate, polyethylene glycol (23) isostearate, polyethylene        glycol (24) isostearate, polyethylene glycol (25) isostearate,        polyethylene glycol (12) oleate, polyethylene glycol (13)        oleate, polyethylene glycol (14) oleate, polyethylene        glycol (15) oleate, polyethylene glycol (16) oleate,        polyethylene glycol (17) oleate, polyethylene glycol (18)        oleate, polyethylene glycol (19) oleate, polyethylene        glycol (20) oleate.

An ethoxylated alkyl ether carboxylic acid or salt thereof which canadvantageously be used is sodium laureth-11 carboxylate. An alkyl ethersulfate which can advantageously be used is sodium laureth-14 sulfate.An ethoxylated cholesterol derivative which can advantageously be usedis polyethylene glycol (30) cholesteryl ether. Polyethylene glycol (25)soyasterol has also proven successful. Ethoxylated triglycerides whichcan advantageously be used are the polyethylene glycol (60) eveningprimrose glycerides.

It is furthermore advantageous to select the polyethylene glycolglycerol fatty acid esters from the group consisting of polyethyleneglycol (20) glyceryl laurate, polyethylene glycol (21) glyceryl laurate,polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23)glyceryl laurate, polyethylene glycol (6) glyceryl caprate/caprinate,polyethylene glycol (20) glyceryl oleate, polyethylene glycol (20)glyceryl isostearate, polyethylene glycol (18) glyceryl oleate/cocoate.

It is likewise favourable to select the sorbitan esters from the groupconsisting of polyethylene glycol (20) sorbitan monolaurate,polyethylene glycol (20) sorbitan monostearate, polyethylene glycol (20)sorbitan monoisostearate, polyethylene glycol (20) sorbitanmonopalmitate, polyethylene glycol (20) sorbitan monooleate.

Optional W/O emulsifiers, but ones which may nevertheless beadvanta-geous for the purposes of the invention can be the following:

-   -   fatty alcohols having from 8 to 30 carbon atoms, monoglycerol        esters of saturated and/or unsaturated, branched and/or        unbranched alkanecarboxylic acids having a chain length of from        8 to 24 carbon atoms, in particular 12-18 carbon atoms,        diglycerol esters of saturated and/or unsaturated, branched        and/or unbranched alkanecarboxylic acids having a chain length        of from 8to 24 carbon atoms, in particular 12-18 carbon atoms,        monoglycerol ethers of saturated and/or unsaturated, branched        and/or unbranched alcohols having a chain length of from 8 to 24        carbon atoms, in particular-12-18 carbon atoms, diglycerol        ethers of saturated and/or unsaturated, branched and/or        unbranched alcohols having a chain length of from 8 to 24 carbon        atoms, in particular 12-18 carbon atoms, propylene glycol esters        of saturated and/or unsaturated, branched and/or unbranched        alkanecarboxylic acids having a chain length of from 8 to 24        carbon atoms, in particular 12-18 carbon atoms, and sorbitan        esters of saturated and/or unsaturated, branched and/or        unbranched alkanecarboxylic acids having a chain length of from        8 to 24 carbon atoms, in particular 12-18 carbon atoms.

Particularly advantageous W/O emulsifiers are glyceryl monostearate,glyceryl monoisostearate, glyceryl monomyristate, glyceryl monooleate,diglyceryl monostearate, diglyceryl monoisostearate, propylene glycolmonostearate, propylene glycol monoisostearate, propylene glycolmonocaprylate, propylene glycol monolaurate, sorbitan monoisostearate,sorbitan monolaurate, sorbitan monocaprylate, sorbitan monoisooleate,sucrose distearate, cetyl alcohol, stearyl alcohol, arachidyl alcohol,behenyl alcohol, isobehenyl alcohol, selachyl alcohol, chimyl alcohol,polyethylene glycol (2) stearyl ether (steareth-2), glycerylmonolaurate, glyceryl monocaprinate and glyceryl monocaprylate.

Preferred compositions according to the invention are particularlysuitable for protecting human skin against ageing processes and againstoxidative stress, i.e. against damage by free radicals, as are produced,for example, by sunlight, heat or other influences. In this connection,they. are in the various administration forms usually used for thisapplication. For example, they may, in particular, be in the form of alotion or emulsion, such as in the form of a cream or milk (O/W, W/O,O/W/O, W/O/W), in the form of oily-alcoholic, oily-aqueous oraqueous-alcoholic gels or solutions, in the form of solid sticks or maybe formulated as an aerosol.

The composition may comprise cosmetic adjuvants which are usually usedin this type of composition, such as, for example, thickeners,softeners, moisturisers, surfactants, emulsifiers, preservatives,antifoams, perfumes, waxes, lanolin, propellants, dyes and/or pigmentswhich colour the composition itself or the skin, and other ingredientsusually used in cosmetics.

The dispersant or solubiliser used can be an oil, wax or other fattysubstance, a lower monoalcohol or lower polyol or mixtures thereof.Particularly preferred monoalcohols or polyols include ethanol,isopropanol, propylene glycol, glycerol and sorbitol.

A preferred embodiment of the invention is an emulsion in the form of aprotective cream or milk which, apart from the compound(s) according tothe invention, comprises, for example, fatty alcohols, fatty acids,fatty acid esters, in particular triglycerides of fatty acids, lanolin,natural and synthetic oils or waxes and emulsifiers in the presence ofwater.

Further preferred embodiments are oily lotions based on natural orsynthetic oils and waxes, lanolin, fatty acid esters, in particulartriglycerides of fatty acids, or oily-alcoholic lotions based on a loweralcohol, such as ethanol, or a glycerol, such as propylene glycol,and/or a polyol, such as glycerol, and oils, waxes and fatty acidesters, such as triglycerides of fatty acids.

The composition according to the invention may also be in the form of analcoholic gel which comprises one or more lower alcohols or polyols,such as ethanol, propylene glycol or glycerol, and a thickener, such assiliceous earth. The oily-alcoholic gels also comprise natural orsynthetic oil or wax.

The solid sticks consist of natural or synthetic waxes and oils, fattyalcohols, fatty acids, fatty acid esters, lanolin and other fattysubstances.

If a composition is formulated as an aerosol, the customary propellants,such as alkanes, fluoroalkanes and chlorofluoroalkanes, are generallyused.

The cosmetic composition may also be used to protect the hair againstphotochemical damage in order to prevent changes of colour shade,bleaching or damage of a mechanical nature. In this case, a suitableformutation is in the form of a rinse-out shampoo, lotion, gel oremulsion, the composition in question being applied before or aftershampooing, before or after colouring or bleaching or before or afterpermanent waving. It is also possible to select a composition in theform of a lotion or gel for styling or treating the hair, in the form ofa lotion or gel for brushing or blow-waving, in the form of a hairlacquer, permanent waving composition, colorant or bleach for the hair.Besides the compound(s) of the formula I, the composition havinglight-protection properties may comprise various adjuvants used in thistype of composition, such as surfactants, thickeners, polymers,softeners, preservatives, foam stabilisers, electrolytes, organicsolvents, silicone derivatives, oils, waxes, antigrease agents, dyesand/or pigments which colour the composition itself or. the hair, orother ingredients usually used for hair care.

The present invention furthermore relates to a process for thepreparation of a composition which is characterised in that at least-onecompound of the formula I containing radicals as described above ismixed with a cosmetically or dermatologically or food-suitable carrier,and to the use of a compound of the formula I for the preparation of acomposition.

The compositions according to the invention can be prepared here withthe aid of techniques which are well known to the person skilled in theart.

The mixing can result in dissolution, emulsification or dispersal of thecompound of the formula I in the carrier.

In a process preferred in accordance with the invention, the compound ofthe formula I is prepared by cyclisation of a correspondinglysubstituted o-hydroxyacetophenone using an anhydride or using an acylchloride under basic conditions. The acyl protecting groups cansubsequently be removed. The reaction here can be carried outanalogously to Kelly, T; Kim M. H.; J. Org. Chem. 1992, 57, 1593-97.Alternatively, the free hydroxyl groups are acylated, followed by aBaker-Venkatamaran rear-rangement under basic conditions with subsequentring closure under acidic conditions. Corresponding reactions,adaptation of which to the compounds desired here presents absolutely noproblems to the person skilled in the art, are disclosed in the patentapplication WO 2002/060889.

Conventional reactions on the ring system or derivatisation of thefunctional groups enable further derivatives of the formula I to beobtained. The reaction condition necessary for such reactions, such as,for example, oxidations, reductions, transesterifications,etherifications, can easily be found by a person skilled in the art forsyntheses of this type in the generally available literature on organicreactions.

It has also been noted that compounds of the formula I can have astabilising effect on the composition. When used in correspondingproducts, the latter are thus also stable for longer and do not changetheir appearance. In particular, the effectiveness of the ingredients,for example vitamins, is retained even in the case of application overextended periods or extended storage. This is, inter alia, particularlyadvantageous in the case of compositions for protecting the skin againstthe effect of UV rays since these cosmetics are exposed to particularlyhigh stresses by UV radiation.

The positive effects of compounds of the formula I give rise to theirparticular suitability for use in cosmetic or pharmaceuticalcompositions.

The properties of compounds of the formula I should likewise be regardedas positive for use in foods or as food supplements or as functionalfoods. The further explanations given for foods also applycorrespondingly to food supplements and functional foods.

The foods which can be enriched with one or more compounds of theformula I in accordance with the present invention include all materialswhich are suitable for consumption by animals or consumption by humans,for example vitamins and provitamins thereof, fats, minerals or aminoacids. (The foods may be solid, but also liquid, i.e. in the form of abeverage). The present invention accordingly furthermore relates to theuse of a compound of the formula I as food additive for human or animalnutrition, and to compositions which are foods or food supplements andcomprise corresponding excipients.

Foods which can be enriched with one or more compounds of the formula Iin accordance with the present invention are, for example, also foodswhich originate from a single natural source, such as, for example,sugar, unsweetened juice, squash or puree of a single plant species,such as, for example, unsweetened apple juice (for example also amixture of different. types of apple juice), grapefruit juice, orangejuice, apple compote, apricot squash, tomato juice, tomato sauce, tomatopuree, etc. Further examples of foods which can be enriched with one.ormore compounds of the formula I in accordance with the present inventionare corn or cereals from a single plant species and materials producedfrom plant species of this type, such as, for example, cereal syrup, ryeflour, wheat flour or oat bran. Mixtures of foods of this type are alsosuitable for being enriched with one or more compounds of the formula Iin accordance with the present invention, for example multivitaminpreparations, mineral mixtures or sweetened juice. As further examplesof foods which can be enriched with one or more compounds of the formulaI in accordance with the present invention, mention may be made of foodcompositions, for example prepared cereals, biscuits, mixed drinks,foods prepared especially for children, such as yoghurt, diet foods,low-calorie foods or animal feeds.

The foods which can be enriched with one or more compounds of theformula I in accordance with the present invention thus include alledible combinations of carbohydrates, lipids, proteins, inorganicelements, trace elements, vitamins, water or active metabolites ofplants and animals.

The foods which can be enriched with one or more compounds of theformula I in accordance with the present invention are preferablyadministered orally, for example in the form of meals, pills, tablets,capsules, powders, syrup, solutions or suspensions.

The foods according to the invention enriched with one or more compoundsof the formula I can be prepared with the aid of techniques which arewell known to the person skilled in the art.

Due to their action, compounds of the formula I are also suitable asmedicament ingredients. Compounds of the formula I can be used, forexample, for preventative treatment of inflammation and allergies of theskin and in certain cases for preventing certain types of cancer.Compounds of the formula I are particularly suitable for the preparationof a medicament for the treatment of inflammation, allergies andirritation, in particular of the skin. It is furthermore possible toprepare medicaments which act as a vein tonic, as cuperose inhibitor, aschemical, physical or actinic erythema inhibitor, as agent for thetreatment of sensitive skin, as decongestant, as desiccant, as slimmingagent, as anti-wrinkle agent, as stimulator for the synthesis ofcomponents of the extracellular matrix, as strengthening agent forimproving skin elasticity, and as anti-ageing agent. Furthermore,compounds of the formula I which are preferred in this connectionexhibit antiallergic and antiinflammatory and antiirritative actions.They are therefore suitable for the preparation of medicaments for thetreatment of inflammation or allergic reactions.

The invention is explained in greater detail below by means of examples.The invention can be carried out throughout the range claimed and is notrestricted to the examples given here.

EXAMPLES Example 1

Preparation of 2-ethoxycarbonyl-7-hydroxychromone

Sodium (7.6 g, 330 mmol) is initially introduced under an Ar atmosphere,and ethanol (500 ml) is slowly added dropwise. The mixture is stirredfor approximately a further 1 hour until the. sodium has completelydissolved and is subsequently cooled to RT using an ice bath.2′,4′-Dihydroxyacetophenone (10 g, 66 mmol) and diethyl oxalate (36 ml,266 mmol) dissolved in 60 ml of EtOH (brown-orange clear solution) areadded dropwise. The solution is stirred at 70° C. for 2 hours. The clearsolution is cooled to 0° C. using an ice/water bath and adjusted from pH13 to pH 4 using about 50 ml of HCl (c=32%). Some of the ethanol is thenremoved from the suspension under reduced pressure. The remainingsuspension is added to 300 ml of ice-water and extracted with CH₂Cl₂,the aqueous phase is extracted by shaking 2× with CH₂Cl₂, the org.phases are combined, extracted 3× with deionised water and 1× withsaturated NaCl solution, and the org. phase is dried using Na sulfate,filtered and evaporated to dryness. Yield: 29.1 g of red-brownslurry-like solid. 100 ml of acetic acid and 1 ml of conc. sulfuric acidare added to the crude product, and the mixture is refluxed for 2 hourswith stirring and cooled, and the solid which precipitates in theprocess is filtered off via a suction filter, washed with a littleCH₃COOH and subsequently with deionised water until neutral and driedovernight in a vacuum drying cabinet at 40° C. and 200 mbar.

Yield: 10.1 g=65.6% of theory of pale-pink pulverulent solid.

Recrystallisation is carried out from a mixture of toluene and methanol.

Yield: 6.6 g=42.9% of theory of beige, fine crystals (HPLC=100%).

¹H NMR (300 MHz) in DMSO δ (ppm): 1.35 (t, 3H), 4.37 (q, 2H), 6.84 (s,1H), 6.9 (d, 1H), 6.96 (dd, 1H), 7.9 (d, 1H), 11.0 (bs, 1OH).

-   -   MS (m/e): 234 (M⁺)

Example 2

Preparation of 7-hydroxy-4-oxo-4H-chromone-2-carboxylic Acid

2-Ethoxycarbonyl-7-hydroxychromone (14.5 g, 62 mmol) is initiallyintroduced dissolved in ethanol (400 ml) at 50° C., and sodium carbonate(20 g, 190 mmol) dissolved in deionised H₂O (200 ml) is added dropwise.The mixture is refluxed at 80° C. for 3 hours with stirring. Aftercooling, the mixture is acidified using 2N HCl. The precipitated whitesolid is filtered off with suction, washed until neutral and dried.

Yield: 6.5 g=50.9% of theory of a virtually white powder;

¹H NMR (300 MHz) in DMSO δ (ppm): 6.8 (s, 1H), 6.9 (d, 1H), 6.95 (dd,1H), 7.9 (d, 1H), 11.0 (bs, 10H), 14.5 (bs, 1COOH)

MS (m/e): 206 (M⁺)

Example 2a

Preparation of 1-ethylhexyl 7-hydroxy-4-oxo-4H-chromone-2-carboxylate

The ester is obtained by esterification of the acid from Example 2 using1-ethylhexyl alcohol.

¹H NMR (300 MHz) in CDCl₃ δ (ppm): 0.79-0.88 (m, 6H), 1.18-1.37 (m, 8H),1.65 (ddd; 1H), 7.02-7.06 (m, 1H+2H arom.), 8.02 (d, 1H arom.)

Example 3

Preparation of 2-methoxy-7-hydroxy-4H-chromen-4-one

Ethyl 7-hydroxychromen-4-one-2-carboxylate (2 g, 8.538 mmol) andgranulated and dried calcium chloride (1 g, 9.01 mmol) are initiallyintroduced, and ethanol (absolute, 40 ml) is added. Sodium borohydride(1.33 g, 35.157 mmol) is subsequently added in portions with icecooling. The reaction mixture is stirred at RT for 2 hours, then againcooled using an ice bath, and sodium borohydride (0.45 g, 11.895 mmol)is again added. The mixture is stirred overnight at RT.

The ethanol is subsequently removed in a rotary evaporator (bathtemperature: 50° C.), 60 ml of deionised water are carefully added tothe residue, and the suspension is acidified dropwise using 2N HCl.About 100 g of ice are subsequently added to the solution, and themixture is stirred for half an hour, during which a white solidprecipitates, which is filtered off with suction and dried at 45° C. ina vacuum drying cabinet. 1.1 g of white solid. Yield: 67%

¹H NMR in DMSO δ (ppm): 4.4 (s, 2H), 6.2 (s, 1H), 6.8 (d, 1H), 6.9 (dd,1H), 7.9 (d, 1H).

MS (m/e): 192 (M⁺);

Example 4

Preparation of 5,7-dihydroxy-4-oxo-4H-chromene-2-carboxylic Acid

Step 1:

2,4,6-Trihydroxyacetophenone dissolved in pyridine is initiallyintroduced under an argon atmosphere, and a little4-(dimethylamino)pyridine (catalytic amount) is introduced. The ethylchloroformylformate is then slowly added dropwise. When everything hasbeen added, the apparatus is heated to 80° C. using an oil bath andstirred at this temperature for 2 hours.

The apparatus is allowed to cool to room temperature, the dark-brownsuspension is added to about 200 ml of ice-water, 200 ml of CH₂Cl₂ areadded, and the mixture is extracted. The aqueous phase is extracted byshaking a further 2× with 50 ml of CH₂Cl₂, and the black org. phases arecombined and washed 2× with 50 ml of deionised water, 3× with 2 molarHCl (pyridine-free) and 1× with saturated NaCl solution, leaving a clearblack-brown org. phase, which is dried using Na₂SO₄. The organic phaseis passed through a glass frit with a little silica gel # 7734 slurriedin CH₂Cl₂/EEE (5:1), the filter cake is rinsed with about 250 ml ofCH₂Cl₂/EEE (5:1), and the solution is evaporated in a rotary evaporator.Yield: 8.5 g of yellow solid. This solid is used as it is for the nextstep.Step 2:

2-Ethoxycarbonyl-7-ethoxyoxalyloxy-4-oxo-4H-chromen-5-yl ethyl oxalatefrom Step 1 dissolved in ethanol is initially introduced at roomtemperature, and Na₂CO₃ dissolved in deionised H₂O is added dropwise.The mixture is subsequently heated to 70° C. and stirred at thistemperature for a further 4 hours. After cooling, 100 ml of ethylacetate are added to the reaction mixture, which is slightly acidifiedusing 1N HCl. The aqueous phase is separated off and extracted. The org.phases are combined, washed 3× with deionised H₂O and 1× with sat. NaClsolution, dried using Na₂SO₄, filtered and evaporated in a rotaryevaporator. Recrystallisation gives 0.4 g of yellow fine crystals(HPLC=98.4%).

¹H NMR (300 MHz) in DMSO δ (ppm): 6.2 (d, 1H), 6.4 (d, 1H), 6.8 (s, 1H),11.1 (bs, 1H), 12.5 (bs, 1H).

MS (m/e): 222 (M⁺)

Example 4

Preparation of 1-ethylhexyl5,7-dihydroxy-4-oxo-4H-chromene-2-carboxylate

The ester is obtained by esterification of the acid from Example 4 using1-ethylhexyl alcohol.

Example 5

Preparation of 5,7-diacetoxy-3-acetyl-2-methylchromen-4-one

2,4,6-Trihydroxyacetophenone dissolved in acetic anhydride is initiallyintroduced, and sodium acetate is added. The suspension is refluxed withstirring for 10 hours. The reaction mixture is subsequently poured intoabout 300 ml of ice-water and extracted 2× with ethyl acetate (EA), andthe org. phases are combined and washed 3× with deionised H₂O. Thesolution which remains is washed further with Na₂HCO₃ solution. Theorganic phase is dried over Na₂SO₄, filtered and evaporated in a rotaryevaporator.

¹H NMR (300 MHz) in DMSO δ (ppm): 7.1 (d, 1H), 7.4 (d, 1H)

MS (m/e). 318 (M⁺)

Example 6

Preparation of 5,7-dihydroxy-2-methylchromen-4-one

5,7-Diacetoxy-3-acetyl-2-methylchromen4-one is refluxed for 1 hour with40 ml of 10% sodium carbonate solution. After cooling, the suspension isadjusted to a pH of about 6 using 2N HCl and cooled. The precipitate isfiltered off, giving 0.6 g of very pale brown powder (T_(M)=279.9° C.)

¹H NMR (300 MHz) in DMSO δ (ppm): 2.3 (s, 3H), 6.15 (s, 1H), 6.18 (d,1H), 6.3 (d, 1H), 10.8 (bs, 1OH), 12.8 (s, 1OH)

MS (m/e): 192 (M⁺)

Example 7

Preparation of 5,7-dihydroxy-2-ethylpentylchromen-4-one

1st Step:

2,4,6-Trihydroxyacetophenone (5 g, 26.3 mmol) is added to 90 ml oftoluene, and 14 g of potassium carbonate dissolved in 70 ml of deionisedwater and 1 g of tetra-n-butylammonium hydrogensulfate are added to thesolution. 2-Ethylhexanoyl chloride (20.5 ml, 119.7 mmol) is addeddropwise to the two-phase mixture over the course of 10 minutes withvigorous stirring. The two-phase mixture is subsequently heated at 70°C. for 5 hours with stirring.

The upper dark-red organic phase is subsequently separated off, theaqueous phase is extracted by shaking twice with dichloromethane, andthe organic phases are combined, washed with saturated sodium chloridesolution, dried over sodium sulfate, filtered and evaporated to drynessin a Rotavapor (bath temperature: 50° C.).

M(R): 19.3 g

2nd Step

19.3 g of the product from the 1st step are dissolved in 600 ml of THF,and lithium hydroxide (4.4 g, 183.7 mmol) is added. The mixture issubsequently refluxed for 5.5 hours. The red-brown reaction solution ispoured onto about 800 g of ice+100 ml of conc. HCl and extracted anumber of times with dichloromethane, and the orange combined organicphases are washed with saturated sodium chloride solution, dried oversodium sulfate, filtered and evaporated to dryness in a rotaryevaporator (bath temperature: 50° C.).

M(R): 17.2 g

3rd Step:

17.2 g of the product from the 2nd step are dissolved in 200 ml ofacetic acid, and 2 ml of conc. sulfuric acid are added. The mixture issubsequently refluxed for 7 hours with stirring. The red-brown cloudysolution is poured onto about 500 g of ice, the red-brown precipitatedsolid is filtered off via a suction filter, taken up in dichloromethaneand, together with the aqueous filtrate, extracted a number of times byshaking with dichloromethane, and the combined organic phases are washedwith saturated sodium chloride solution, dried over sodium sulfate,filtered and evaporated to dryness in a rotary evaporator (bathtemperature: 50° C.).

m(R): 18.4 g of residue, TLC: one spot

The residue is dissolved in a little methanol, and deionised water isadded, whereupon a beige solid precipitates, which is filtered off via asmall suction filter.

m(K): 1.65 g of beige solid

The filtrate is evaporated again, and 100 ml of heptane are added to thedistillation residue, whereupon a solid precipitates, which is filteredoff via a suction filter.

m(K2): 2.27 9 of pale-brown solid

m(K tot.): 3.92 g are 52.3% of the theoretical yield, based on theamount of 2,4,6-trihydroxyacetophenone used.

¹H NMR (300 MHz) in DMSO δ (ppm): 0.9 (m, 6H), 1.15-1.3 (m, 4H),1.55-1.65 (m, 4H), 2.45 (q, 1H), 6.17 (s, 1H), 6.2 (d, 1H), 6.35 (d,1H), 10.75 (bs, OH), 12.85 (s, OH).

MS (m/e): 276 (M⁺)

The following is prepared analogously:5,7-dihydroxy-3-(2-methoxyacetyl)-2-methoxymethylchromen-4-one.

Example 8

Preparation of 7-isopropyl-4-oxo-4H-chromone-3-carbaldehyde

7-Hydroxy-4-oxo4H-chromone-3-carbaldehyde (2 g, 10.5 mmol) is dissolvedin N,N-dimethylformamide (25 ml) under an N₂ atmosphere, potassiumcarbonate (1.8 g, 13 mmol) and potassium iodide (50 mg) are added, andthe mixture is stirred at RT for 1 hour. 2-Bromopropane (2 ml, 21 mmol)is then slowly added dropwise, and the mixture is heated at 55° C. for 2hours. A further 2 ml of 2-bromopropane are added, and the mixture isstirred at 55° C. for a further 2.5 hours. After stirring at RT for 12hours, the reaction mixture is introduced into 60 ml of deionised water,acidified using dilute HCl and extracted with 150 ml of EA. The aqueousphase is extracted a further 2× with EA. The combined org. phases areextracted by shaking 2× with 150 ml. of deionised water and 1× withsaturated NaCl solution, dried using Na sulfate and filtered, and thesolvent is stripped off. For purification, the crude product isdissolved in 10 ml of eluent (CH₂Cl₂/MeOH 9.5/0.5) and filtered through250 g of silica gel #109385. Yield: 281 mg =11.52% of theory. (HPLCcontent: 89.3%).

¹H NMR (300 MHz) in DMSO δ (ppm): 1.3 (d, 6H), 4.9 (m, 1H), 7.1 (dd,1H), 7.3 (d, 1H), 8.85 (s, 1H), 10.1 (s, 1H).

Example 9

Preparation of L-ascorbyl6-[5,7-dihydroxy-4-oxo-4H-chromone-2-carboxylate]

5,7-Dihydroxy-4-oxo-4H-chromone-2-carboxylic acid (400 mg, 1.8 mmol)dissolved in 95-97% sulfuric acid (10 ml) is initially introduced underan argon atmosphere and warmed to 55° C. Ten 100 mg portions ofL-(+)-ascorbic acid are introduced slowly, during which the temperatureis held at a maximum of 75° C. The mixture is subsequently stirred atthis temperature for 12 hours.

The reaction mixture is cooled using an ice bath and introduced into 50ml of ice-water, EA is added, the mixture is filtered through Celite,the aqueous phase is separated off and extracted again with a little EA,and the org. phases are combined, washed 4× with about 20 ml ofdeionised H₂O each time and 1× with sat. NaCl solution until neutral,dried using Na₂SO₄, filtered and evaporated in a rotary evaporator.

Yield: 250 mg

HPLC-ESI-MS shows [M+H]⁺=365.1

Example 10

Investigations of Efficacy

Example 10a

Antiinflammatory Properties (PGE2 Assay)

Human keratinocytes of the cell line NCTC R13 are pre-cultivated for 24hours at 37° C. in a 5% CO₂ atmosphere with DMEM culture medium (LifeTechnologies). The cells are treated with LU for 24 hours, and theculture medium is then removed. A fresh culture medium containing theinflammation-triggering active ingredient phorbol myristate acetate(PMA; 0.1 g/ml) and LU is added. After incubation for 24 hours, theculture medium is collected.and analysed. By means of an ELISA DE0100kit (R&D Systems), the release is used in order to investigate therelease of the inflammation marker prostaglandin E2 (PGE2) (Table).TABLE PGE2 release from human keratinocytes Control Neg. 0.2 mM 0.04 mM0.008 mM (only control LU LU LU PMA) (no PMA) PGE2 6.31 226.39 340.62302.02 0.018 (ng/ml) Number of 3 3 3 3 3 tests Standard 0.5 11.92 17.939.31 0.001 deviation % compared 2 75 113 100 0 with control

5,7-Dihydroxy-2-methylchromen-4-one in doses of 0.2 mM and 0.04 mMexhibits a clear reduction in PGE2 release on exposure to PMA.

Example 10b

Action on the Activity of Leukocyte Elastase

5,7-Dihydroxy-2-methylchromen-4-one-in TRIS buffer (500 mM) is incubatedfor 10 minutes on ice with elastase (from human leukocytes; Sigma E8140;100 mU/well). 5 pg/well of elastin are subsequently added, and theplates are incubated at 37° C. for 2 hours. The fluorescence isdetermined using a Spectromax Gemini spectrometer (Molecular Devices) atλex=485 nm and λem=538 nm. TABLE Leukocyte elastase activity Control 200μM (0.1 mM Neg. LU 40 μM LU AAPV) control Fluorescence 1096.4 2195.996.0 2430.2 intensity Number of 3 3 3 3 tests Standard 53 33 7 62deviation % compared 45 90 4 100 with control % quenching 19 0 0 —Inhibition (%) 45 10 96 —

5,7-Dihydroxy-2-methylchromen-4-one in doses of 200 μM and 40 μMexhibits clear inhibition of the elastase activity.

Example 10c

Action on the Activity of Hyaluronidase

5,7-Dihydroxy-2-methylchromen-4-one in phosphate buffer (0.1 M) ispre-incubated with hyaluronidase (HYAL, Sigma type IV-S, H3884; 1 mg/lin phosphate buffer (0.1 M)). Hyaluronic acid (HA, Sigma H-1876; 1.2mg/ml) is subsequently added, and the mixture is incubated at 37° C. for1 hour.

The remaining hyaluronic acid (HA) is subsequently precipitated usingserum albumen (BSA, Sigma A7888) and determined photometrically. TABLEHyaluronidase activity Control 6.25 3.125 (only HA, 25 mM 12.5 mM mM noControl LU mM LU LU LU enzyme) (no LU) Hyaluronidase 37 63 81 91 0 100activity Hyaluronidase 63 37 19 9 — 0 inhibition

5,7-Dihydroxy-2-methylchromen-4-one in the doses investigated exhibitsclear inhibition of hyaluronidase activity. 50% inhibition (IC₅₀) isachieved at about 20 mM of 5,7-dihydroxy-2-methylchromen-4-one.

Example 11

Compositions

Formulations for cosmetic compositions comprising compounds according toExamples 1-3 are shown by way of example below. The INCl names of thecommercially available compounds are also shown.

UV-Pearl, OMC stands for the composition having the INCl name: Water(for EU: Aqua), Ethylhexyl Methoxycinnamate, Silica, PVP, Chlorphenesin,BHT; this composition is commercially available under the nameEusolex®UV Pearl™ OMC from Merck KGaA, Darmstadt.

The other UV Pearl products indicated in the tables are each ofanalogous composition with OMC replaced by the UV filter indicated.TABLE 1 W/O emulsions (data in % by weight) 1-1 1-2 1-3 1-4 1-5 1-6 1-71-8 1-9 1-10 Titanium Dioxide 2 5 3 2-Methyl-5,7-dihydroxy- 5 3 2 1 2 11 chromen-4-one 2-(1-Ethylhexyl)-5,7- 1 2 1 dihydroxychromen-4-one ZincOxide 5 2 UV-Pearl, OMC 30 15 15 15 15 15 15 15 15 15Polyglyceryl-3-Dimerate 3 3 3 3 3 3 3 3 3 3 Cera Alba 0.3 0.3 0.3 0.30.3 0.3 0.3 0.3 0.3 0.3 Hydrogenated Castor Oil 0.2 0.2 0.2 0.2 0.2 0.20.2 0.2 0.2 0.2 Paraffinium Liquidum 7 7 7 7 7 7 7 7 7 7 Caprylic/CapricTriglyceride 7 7 7 7 7 7 7 7 7 7 Hexyl Laurate 4 4 4 4 4 4 4 4 4 4PVP/Eicosene Copolymer 2 2 2 2 2 2 2 2 2 2 Propylene Glycol 4 4 4 4 4 44 4 4 4 Magnesium Sulfate 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6Tocopherol 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Tocopheryl Acetate0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Cyclomethicone 0.5 0.5 0.5 0.50.5 0.5 0.5 0.5 0.5 0.5 Propylparaben 0.05 0.05 0.05 0.05 0.05 0.05 0.050.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.150.15 0.15 Water to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100to 100 to 100 1-11 1-12 1-13 1-14 1-15 1-16 1-17 1-18 Titanium Dioxide 32 3 2 5 Benzylidene Malonate Polysiloxane 1 0.5 MethyleneBis-benzotriazolyl 1 1 0.5 Tetramethylbutylphenol2-(1-Ethylhexyl)-5,7-dihydroxy- 5 3 2 5 1 3 7 2 chromen-4-onePolyglyceryl-3-Dimerate 3 3 3 3 Cera Alba 0.3 0.3 0.3 0.3 2 2 2 2Hydrogenated Castor Oil 0.2 0.2 0.2 0.2 Paraffinium Liquidum 7 7 7 7Caprylic/Capric Triglyceride 7 7 7 7 Hexyl Laurate 4 4 4 4 PVP/EicoseneCopolymer 2 2 2 2 Propylene Glycol 4 4 4 4 Magnesium Sulfate 0.6 0.6 0.60.6 Tocopherol 0.5 0.5 0.5 0.5 Tocopheryl Acetate 0.5 0.5 0.5 0.5 1 1 11 Cyclomethicone 0.5 0.5 0.5 0.5 Propylparaben 0.05 0.05 0.05 0.05 0.050.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15Dicocoyl Pentyerythrityl Citrate 6 6 6 6 (and) Sorbitan Sesquioleate(and) Cera Alba (and) Aluminium Stearate PEG-7 Hydrogenated Castor Oil 11 1 1 Zinc Stearate 2 2 2 2 Oleyl Erucate 6 6 6 6 Decyl Oleate 6 6 6 6Dimethicone 5 5 5 5 Tromethamine 1 1 1 1 Glycerine 5 5 5 5 Allantoin 0.20.2 0.2 0.2 Water to 100 to 100 to 100 to 100 to 100 to 100 to 100 to100 1-19 1-20 1-21 1-22 1-23 1-24 1-25 1-26 1-27 1-28 1-29 TitaniumDioxide 2 5 3 3 Benzylidene Malonate 1 1 1 Polysiloxane Zinc Oxide 5 22-Methyl-5,7-dihydroxychromen-4- 5 5 5 5 7 5 5 5 5 5 8 one UV-Pearl, OCR10 5 UV-Pearl, 10 EthylhexylDimethylPABA UV-Pearl, Homosalate 10UV-Pearl, Ethylhexyl Salicylate 10 UV-Pearl, OMC. BP-3 10 UV-Pearl, OCR.BP-3 10 UV-Pearl, Ethylhexyl Dimethyl 10 PABA, BP-3 UV-Pearl,Homosalate, BP-3 10 UV-Pearl, Ethylhexyl Salicylate, 10 BP-3 BMDBM 2UV-Pearl, OMC, 25 4-Methylbenzylidene Camphor Polyglyceryl-3-Dimerate 33 3 3 3 3 3 3 3 3 3 Cera Alba 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.30.3 Hydrogenated Castor Oil 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2Paraffinium Liquidum 7 7 7 7 7 7 7 7 7 7 7 Caprylic/Capric Triglyceride7 7 7 7 7 7 7 7 7 7 7 Hexyl Laurate 4 4 4 4 4 4 4 4 4 4 4 PVP/EicoseneCopolymer 2 2 2 2 2 2 2 2 2 2 2 Propylene Glycol 4 4 4 4 4 4 4 4 4 4 4Magnesium Sulfate 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 Tocopherol0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Tocopheryl Acetate 0.5 0.50.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Cyclomethicone 0.5 0.5 0.5 0.5 0.50.5 0.5 0.5 0.5 0.5 0.5 Propylparaben 0.05 0.05 0.05 0.05 0.05 0.05 0.050.05 0.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.15 0.15 0.15 0.150.15 0.15 0.15 0.15 Water to 100

TABLE 2 O/W emulsions, data in % by weight 2-1 2-2 2-3 2-4 2-5 2-6 2-72-8 2-9 2-10 Titanium Dioxide 2 5 3 Methylene Bis-benzotriazolyl 1 2 1Tetramethylbutylphenol 2-(1-Ethylhexyl)-5,7-dihydroxy- 1 2 1 1chromen-4-one 4′-Methoxy-6-hydroxyflavone 1 3 2 5 5 22-(Methoxy-methyl)-5,7- 5 5 5 5 5 5 5 5 5 5 dihydroxychromen-4-one2-Carboxy-5,7-dihydroxy- 1 5 4 6 7 2 1 chromen-4-one 4-MethylbenzylideneCamphor 2 3 4 3 2 BMDBM 1 3 3 3 3 3 3 Stearyl Alcohol (and) Steareth-7 33 3 3 3 3 3 3 3 3 (and) Steareth-10 Glyceryl Stearate (and) Ceteth- 3 33 3 3 3 3 3 3 3 20 Glyceryl Stearate 3 3 3 3 3 3 3 3 3 3 Microwax 1 1 11 1 1 1 1 1 1 Cetearyl Octanoate 11.5 11.5 11.5 11.5 11.5 11.5 11.5 11.511.5 11.5 Caprylic/Capric Triglyceride 6 6 6 6 6 6 6 6 6 6 Oleyl Oleate6 6 6 6 6 6 6 6 6 6 Propylene Glycol 4 4 4 4 4 4 4 4 4 4 GlycerylStearate SE Stearic Acid Persea Gratissima Propylparaben 0.05 0.05 0.050.05 0.05 0.05 0.05 0.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.150.15 0.15 0.15 0.15 0.15 0.15 Tromethamine 1.8 Glycerine Water to 100 to100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 to 100 2-11 2-122-13 2-14 2-15 2-16 2-17 2-18 Titanium Dioxide 3 2 2 5 BenzylideneMalonate Polysiloxane 1 0.5 Methylene Bis-benzotriazolyl 1 1 0.5Tetramethylbutylphenol 4′-Methoxy-7-β-glucoside Flavone 1 22-Carboxyl-5,7-dihydroxychromen-4-one 1 3 2 5 52-Carboxy-7-hydroxychromen-4-one 5 5 5 5 5 5 5 5 Ethyl5,7-Dihydroxychromen-4-one-2- 1 5 4 6 7 carboxylate Zinc Oxide 2UV-Pearl, OMC 15 15 15 30 30 30 15 15 4-Methylbenzylidene Camphor 3BMDBM 1 Phenylbenzimidazole Sulfonic Acid 4 Stearyl Alcohol (and)Steareth-7 3 3 3 3 (and) Steareth-10 Glyceryl Stearate (and) Ceteth-20 33 3 3 Glyceryl Stearate 3 3 3 3 Microwax 1 1 1 1 Cetearyl Octanoate 11.511.5 11.5 11.5 Caprylic/Capric Triglyceride 6 6 6 6 14 14 14 14 OleylOleate 6 6 6 6 Propylene Glycol 4 4 4 4 Glyceryl Stearate SE 6 6 6 6Stearic Acid 2 2 2 2 Persea Gratissima 8 8 8 8 Propylparaben 0.05 0.050.05 0.05 0.05 0.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.15 0.150.15 0.15 0.15 Tromethamine 1.8 Glycerine 3 3 3 3 Water to 100 to 100 to100 to 100 to 100 to 100 to 100 to 100 2-19 2-20 2-21 2-22 2-23 2-242-25 2-26 2-27 2-28 Titanium Dioxide 3 3 2 Benzylidene Malonate 1 2 1 11 0.5 Polysiloxane 7,8,3′,4′-Tetrahydroxyflavone 1 2 1 1 Ethyl5,7-Dihydroxychromen-4- 1 3 2 5 5 2 on-2-carboxylate2-Methyl-5,7-dihydroxy- 5 5 5 5 5 5 5 5 5 5 chromen-4-one MethyleneBis-benzotriazolyl 1 2 1 1 1 0.5 Tetramethylbutylphenol Zinc Oxide 5 2 2UV-Pearl, OMC 15 15 15 15 15 15 15 15 15 15 Caprylic/Capric Triglyceride14 14 14 14 14 14 14 14 14 14 Oleyl Oleate Propylene Glycol GlycerylStearate SE 6 6 6 6 6 6 6 6 6 6 Stearic Acid 2 2 2 2 2 2 2 2 2 2 PerseaGratissima 8 8 8 8 8 8 8 8 8 8 Propylparaben 0.05 0.05 0.05 0.05 0.050.05 0.05 0.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.15 0.15 0.150.15 0.15 0.15 0.15 Glyceryl Stearate. Ceteareth- 20. Ceteareth-10.Cetearyl Alcohol. Cetyl Palmitate Ceteareth-30 Dicaprylyl EtherHexyldecanol, Hexyldexyl Laurate Cocoglycerides Tromethamine Glycerine 33 3 3 3 3 3 3 3 3 Water to 100 to 100 to 100 to 100 to 100 to 100 to 100to 100 to 100 to 100

TABLE 3 Gels, data in % by weight 3-1 3-2 3-3 3-4 3-5 3-6 3-7 3-8 3-93-10 a = aqueous gel Titanium Dioxide 2 5 32-Methyl-5,7-Dihydroxychromen-4- 1 2 1 1 one Ethyl5,7-Dihydroxy-chromen-4- 1 3 2 5 5 2 one-2-carboxylate BenzylideneMalonate 1 1 2 1 1 Polysiloxane Methylene Bis-benzotriazolyl 1 1 2 1Tetramethylbutylphenol Zinc Oxide 2 5 2 UV-Pearl, Ethylhexyl 30 15 15 1515 15 15 15 15 15 Methoxycinnamate 4-Methylbenzylidene Camphor 2Butylmethoxydibenzoylmethane 1 Phenylbenzimidazole Sulfonic 4 AcidPrunus Dulcis 5 5 5 5 5 5 5 5 5 5 Tocopheryl Acetate 0.5 0.5 0.5 0.5 0.50.5 0.5 0.5 0.5 0.5 Caprylic/Capric Triglyceride 3 3 3 3 3 3 3 3 3 3Octyldodecanol 2 2 2 2 2 2 2 2 2 2 Decyl Oleate 2 2 2 2 2 2 2 2 2 2PEG-8 (and) Tocopherol (and) 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.050.05 0.05 Ascorbyl Palmitate (and) Ascorbic Acid (and) Citric AcidSorbitol 4 4 4 4 4 4 4 4 4 4 Polyacrylamide (and) C13-14 3 3 3 3 3 3 3 33 3 Isoparaffin (and) Laureth-7 Propylparaben 0.05 0.05 0.05 0.05 0.050.05 0.05 0.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.15 0.15 0.150.15 0.15 0.15 0.15 Tromethamine 1.8 Water to 100 to 100 to 100 to 100to 100 to 100 to 100 to 100 to 100 to 100

1. A method for caring, preserving or improving the general state ofskin or hair, for prophylaxis against time- and/or light-induced ageingprocesses of the human skin or human hair; for prophylaxis against dryskin, wrinkle formation and/or pigment defects; or for the reduction orprevention of the harmful effects of UV rays on the skin, forprophylaxis against or reduction of skin unevenness, such as wrinkles,fine lines, rough skin or large-pored skin, for the prophylaxis and/orprevention of premature skin ageing; the prophylaxis and/or preventionof light- or ageing-induced wrinkling of the skin; for the reduction ofpigmentation and keratosis actinica; or for the prophylaxis and/ortreatment of a disease that is associated with normal skin ageing orlight-induced ageing of the skin, for the prophylaxis and/or treatmentof a skin disease that is associated with defective keratinisationrelating to differentiation and cell proliferation; for the treatment ofacne vulgaris, acne comedonica, polymorphic acne, acne rosaceae, nodularacne, acne conglobata, age-related acne, acne occurring as a sideeffect, acne solaris, medicament-related acne or acne professionalis;for the treatment of a defect of keratinisation, ichthyosis, anichthyosiform state, Darier's disease, keratosis palmoplantaris,leukoplasia, a leukoplasiform state, skin and mucosal (buccal) eczema(lichen); for the treatment of a skin disease that is associated withdefective keratinisation and has an inflammatory and/or immunoallergiccomponent, or psoriasis relating to the skin, mucous membranes orfinger- or toenails, or psoriatic rheumatism or skin atopy, eczema, orrespiratory atopy, or hypertrophy of the gums, for the prophylaxisand/or treatment of a benign or malignant excrescence of the dermis orepidermis, which may be of viral origin, of verruca vulgaris, verrucaplana, epidermodysplasia verruciformis, oral papillomatosis,papillomatosis florida, or an excrescence that may be caused by UVradiation, or of epithelioma baso-cellulare or epitheliomaspinocellulare, comprising applying to the skin or hair at least onecompound of formula I

or a salt thereof or a composition comprising at least one compound offormula I or a salt thereof, where R¹ and R² are identical or different,and are H, —C(═O)—R⁷, —C(═O)—OR⁷, a straight-chain or branched C₁- toC₂₀-alkyl group, a straight-chain or branched C₃- to C₂₀-alkenyl group,or a straight-chain or branched C₁-to C₂₀-hydroxyalkyl group, where thehydroxyl group is optionally bonded to a primary or secondary carbonatom of the alkyl and wherein the alkyl is optionally interrupted byoxygen, a C₃- to C₁₀-cycloalkyl group, or a C₃- to C₁₂-cycloalkenylgroup, where the cyclic group is optionally bridged by —(CH₂)_(n)—group, where n=1 to 3, R³ is H or a straight-chain or branched C₁- toC₂₀-alkyl group, R⁴ is H or —OR⁸, R⁵ and R⁶ are identical or different,and are H or —OH, a straight-chain or branched C₁- to C₂₀-alkyl group, astraight-chain or branched C₃- to C₂₀-alkenyl group, a straight-chain orbranched C₁- to C₂₀-hydroxyalkyl group, where the hydroxyl group isoptionally bonded to a primary or secondary carbon atom of the alkyl andwherein the alkyl is optionally interrupted by oxygen, R⁷ is H, astraight-chain or branched C₁- to C₂₀-alkyl group, or a polyhydroxylcompound, and R⁸ is H or a straight-chain or branched C₁- to C₂₀-alkylgroup, where at least two of the substituents R¹, R² and R⁴—R⁶ aredifferent from H or at least one substituent from R¹ and R² is —C(═O)—R⁷or —C(═O)—OR⁷.
 2. A method according to claim 1, wherein the method isfor prophylaxis against time- and/or light-induced ageing processes ofthe human skin or human hair; for prophylaxis against dry skin, wrinkleformation and/or pigment defects; or for the reduction or prevention ofthe harmful effects of UV rays on the skin.
 3. A method according toClaim 1, wherein the method is for prophylaxis against or reduction ofskin unevenness, such as wrinkles, fine lines, rough skin or large-poredskin.
 4. A method according to claim 1, wherein the method is for theprophylaxis and/or prevention of premature skin ageing; the prophylaxisand/or prevention of light- or ageing-induced wrinkling of the skin; forthe reduction of pigmentation and keratosis actinica; or for theprophylaxis and/or treatment of a disease that is associated with normalskin ageing or light-induced ageing of the skin.
 5. A method accordingto claim 1, wherein the method is for the prophylaxis and/or treatmentof a skin disease that is associated with defective keratinisationrelating to differentiation and cell proliferation; for the treatment ofacne vulgaris, acne comedonica, polymorphic acne, acne rosaceae, nodularacne, acne conglobata, age-related acne, acne occurring as a sideeffect, acne solaris, medicament-related acne or acne professionalis;for the treatment of a defect of keratinisation, ichthyosis, anichthyosiform state, Darier's disease, keratosis palmoplantaris,leukoplasia, a leukoplasiform state, skin and mucosal (buccal) eczema(lichen); for the treatment of a skin disease that is associated withdefective keratinisation and has an inflammatory and/or immunoallergiccomponent, or psoriasis relating to the skin, mucous membranes orfinger- or toenails, or psoriatic rheumatism or skin atopy, eczema, orrespiratory atopy, or hypertrophy of the gums.
 6. A method according toclaim 1, wherein the method is for the prophylaxis and/or treatment of abenign or malignant excrescence of the dermis or epidermis, which may beof viral origin, of verruca vulgaris, verruca plana, epidermodysplasiaverruciformis, oral papillomatosis, papillomatosis florida, or anexcrescence that may be caused by UV radiation, or of epitheliomabaso-cellulare or epithelioma spinocellulare.
 7. A method according toclaim 1, wherein R³ is H, and R⁴ is OH.
 8. A method according to claim1, wherein R⁵ and R⁶ are H.
 9. A method according to claim 1, whereinone of the radicals R¹ and R² is H and the other radical of R¹ and R² is—C(═O)—R⁷, —C(═O)OR⁷ or a straight-chain or branched C₁- to C₂₀-alkylgroup.
 10. A method according to claim 1, wherein the compound offormula I is a compound of one of the formulae Ia-In:


11. A composition comprising at least one compound of formula I

or a salt thereof or a composition comprising at least one compound offormula I or a salt thereof, where R¹ and R² are identical or different,and are H, —C(═O)—R⁷, —C(═O)—OR⁷, a straight-chain or branched C₁- toC₂₀-alkyl group, a straight-chain or branched C₃- to C₂₀-alkenyl group,or a straight-chain or branched C₁- to C₂₀-hydroxyalkyl group, where thehydroxyl group is optionally bonded to a primary or secondary carbonatom of the alkyl and wherein the alkyl is optionally interrupted byoxygen, a C₃- to C₁₀-cycloalkyl group, or a C₃- to C₁₂-cycloalkenylgroup, where the cyclic group is optionally bridged by —(CH₂)_(n)—group, where n=1 to 3, R³ is H or a straight-chain or branched C₁- toC₂₀-alkyl group, R⁴ is H or OR⁸, R⁵ and R⁶ are identical or different,and are H or —OH, a straight-chain or branched C₁- to C₂₀-alkyl group, astraight-chain or branched C₃- to C₂₀-alkenyl group, a straight-chain orbranched C₁- to C₂₀-hydroxyalkyl group, where the hydroxyl group isoptionally bonded to a primary or secondary carbon atom of the alkyl andwherein the alkyl is optionally interrupted by oxygen, R⁷ is H, astraight-chain or branched C₁- to C₂₀-alkyl group, or a polyhydroxylcompound, and R⁸ is H or a straight-chain or branched C₁- to C₂₀-alkylgroup, where at least two of the substituents R¹, R² and R⁴—R⁶ aredifferent from H or at least one substituent from R¹ and R² is —C(═O)—R⁷or —C(═O)—OR⁷, and at least one skin-care ingredient other than acompound of formula I, and at least one carrier that is suitable fortopical application or is a food-suitable carrier.
 12. A compositionaccording to claim 11, wherein the composition comprises one or morecompounds of formula I in an amount of 0.01 to 20% by weight based onthe composition.
 13. A composition according to claim 11, wherein the atleast one further skin-care ingredient is one or more antioxidantsand/or vitamins.
 14. A composition according to claim 11, furthercomprising one or more UV filters.
 15. A composition according to claim11, wherein the at least one further skin-care ingredient is apyrimidinecarboxylic acid, aryl oxime, or ectoine.
 16. A process forpreparing a composition according to claim 11, comprising mixingtogether at least one compound of formula I, at least one skin careingredient other than a compound of formula I, and at least one carrierthat is suitable for topical application.
 17. A method according toclaim 7, wherein at least one of the radicals R⁵ and R⁶ is OH.
 18. Acomposition according to claim 11, wherein the composition comprises oneor more compounds of formula I in an amount of 0.01 to 10% by weightbased on the composition.
 19. A composition according to claim 11,wherein the at least one skin-care ingredient is vitamin C or aderivative of vitamin C, DL-α-tocopherol, tocopherol E acetate,nicontinic acid, pantothenic acid or biotin.
 20. A composition accordingto claim 11, wherein the composition does not contain a retinolderivative.
 21. A composition according to claim 11, further comprising3-(4′-methylbenzylidene)-dl-camphor,1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione,4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octylmethoxycinnamate, 3,3,5-trimethylcyclohexyl salicylate, 2-ethylhexyl4-(dimethylamino)benzoate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate,2-phenylbenzimidazole-5-sulfonic acid or a potassium, sodium ortriethanolamine salt thereof.
 22. A composition according to claim 11,wherein the at least one carrier that is suitable for topicalapplication is at least one carrier that is a cosmetically ordermatologically or food-suitable carrier.
 23. A method according toclaim 1, wherein the method is for caring, preserving or improving thegeneral state of skin or hair.
 24. A method according to claim 1,wherein R⁷ is an ascorbic acid radical or a glycosidic radical.
 25. Amethod according to claim 1, wherein a composition comprising at leastone compound of formula I or a salt thereof is administered and thecomposition contains at least one compound of formula II or a saltthereof

where R¹ to R¹⁰ are identical or different, and are H OR¹¹ astraight-chain or branched C₁- to C₂₀-alkyl group, a straight-chain orbranched C₃- to C₂₀-alkenyl group, a straight-chain or branched C₁- toC₂₀-hydroxyalkyl group, where the hydroxyl group is optionally bonded toa primary or secondary carbon atom of the alkyl and wherein the alkyl isoptionally interrupted by oxygen, a C₃- to C₁₀-cycloalkyl group, or aC₃- to C₁₂-cycloalkenyl group, where the cyclic group is optionallybridged by —(CH₂)_(n)— group, where n=1 to 3, where all OR¹¹ are,independently of one another, OH a straight-chain or branched C₁- toC₂₀-alkoxy group, a straight-chain or branched C₃- to C₂₀-alkenyloxygroup, a straight-chain or branched C₁- to C₂₀-hydroxyalkoxy group,where the hydroxyl group(s) are optionally bonded to a primary orsecondary carbon atom of the alkyl and wherein the alkyl is optionallyinterrupted by oxygen, a C₃- to C₁₀-cycloalkoxy group, or C₃- toC₁₂-cycloalkenyloxy group, where the cyclic group is optionally bridgedby —(CH₂)_(n)— group, where n=1 to 3, or a mono- or oligoglycosylradical, with the proviso that at least 4 radicals from R¹ to R⁷ are OHand that the compound of formula II contains at least two pairs ofadjacent —OH groups, or R², R⁵ and R⁶ are OH and the radicals R¹, R³, R⁴and R⁷⁻¹⁰ are H.